CYCLIC FORMYL AND CYCLIC KETONE COMPOUNDS, PREPARATION METHOD THEREFOR, AND PHARMACEUTICAL USE

Abstract

The present invention provides a cycloyl formyl and cycloyl ketone compounds, a preparation method therefor, and a pharmaceutical use. The present invention finds that the compounds shown in formula (I) better inhibits Zika virus and dengue virus infection and replication, may be used as a drug for treating and preventing diseases caused by Zika virus and dengue virus, and may also become a drug for treating and preventing diseases caused by other flaviviruses, such as yellow fever, West Nile virus infection, Japanese encephalitis, AIDS caused by HIV etc., and diseases caused by hand, foot and mouth virus infection etc. The compounds may treat disease caused by bacterial infections, including inflammatory bowel disease ulcerative colitis and Crohn's disease, diseases caused by Escherichia coli, diseases caused by Staphylococcus aureus etc., and diseases caused by Acinetobacter baumannii.

Claims

1. Compound having Formula (I): ##STR00165## wherein ring A is selected from a substituted or unsubstituted non-aromatic ring, a non-aromatic heterocyclic ring, a carbon aromatic ring, or an aromatic heterocyclic ring; X.sup.1 and/or X.sup.2 is/are absent or selected from O, S, S(O), S(O.sub.2), NR.sup.8, C(O), (C(R.sup.9R.sup.10)).sub.p, and X.sup.1 and X.sup.2 are not same if selected from O, S, S(O), or S(O.sub.2); Y.sup.1 and Y.sup.2 are the same or different, and Y.sup.1 and Y.sup.2 are independently one of N and CR.sup.11; m and/or n are integers from 0 to 6, and m+n is an integer from 0 to 6; p is an integer from 1 to 6; when one of X.sup.1 or X.sup.2 is NR.sup.8 and the other is absent, Y.sup.1 is N, R.sup.1 comprises one or more of substituted or unsubstituted benzene rings, no cyclic structure is formed between R.sup.2 and R.sup.3 and/or R.sup.4 and/or R.sup.5 and/or R.sup.6 and/or R.sup.7 and/or R.sup.8, and when R.sup.4 and/or R.sup.5 and/or R.sup.7 connecting to N on any of two sides of the formyl group are one or more of acyl group or carbamoyl group or formate group or hydrazide group or alkyl group with six or less carbon atoms, the ring A does not include substituted or unsubstituted pyrrole rings; when one of X.sup.1 or X.sup.2 is absent, Y.sup.1 is N, and a cyclic structure is formed between R.sup.2 and R.sup.4 and/or R.sup.5 and/or R.sup.7 connecting to N on any of two sides of the formyl group, the ring A does not include pyrrole ring and 4-substituted pyrrole ring; R to R.sup.11 are H, CN, CF.sub.3, nitro, halogen, randomly substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclic group, optionally substituted alkoxy, optionally substituted alkylthio, optionally substituted alkylthio monoxide (sulfoxide), optionally substituted alkylthio dioxide (sulfone), optionally substituted sulfonyl, carboxylic acid, carboxylate, optionally substituted ester group, amide, optionally substituted amido group, optionally substituted alkene group, optionally substituted cycloalkene group, optionally substituted arylalkyl group, optionally substituted heterocyclic arylalkyl group, optionally substituted aromatic hydrocarbon group, optionally substituted heterocyclic aromatic hydrocarbon group, optionally substituted aromatic olefin group, optionally substituted heterocyclic aromatic alkene group, wherein the random substituent is selected from halogen, cyano, nitro, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio or C.sub.2-6 alkenyl, carboxyl, carboxylate, sulfonate; when ring A is a pyrrole ring, in a corresponding pyrrole-2-formylhydrazine derivative formed therefrom, there is no other substituent except for R.sup.1, and the R.sup.1 is substituted phenyl or any other substituent with more than four carbons; when ring A is a furan ring or a thiophene ring, in furan-2-carboxamide derivatives and thiophene-2-carboxamide derivatives formed therefrom respectively there is no other substituent except for R.sup.1, and the R.sup.1 is any substituent with more than 4 carbon atoms; wherein: a double bond is formed between X.sup.1 and X.sup.2; a 4- to 6-membered fused ring is formed between X.sup.1 and X.sup.2; a 4- to 6-membered ring is formed between X.sup.1 and R.sup.2; a double bond is formed between X.sup.1 and R.sup.11 and/or Y.sup.1; a 4- to 6-membered ring is formed between X.sup.1 and R.sup.11 and/or Y.sup.1; a 4- to 6-membered ring is formed between R.sup.2 and R.sup.7, or R.sup.2 and R.sup.4, or R.sup.2 and R.sup.5, or R.sup.2 and R.sup.6; a 4- to 6-membered spiro ring is formed between R.sup.2 and R.sup.3; a double bond is formed between vicinal substituents; a ring is formed between vicinal substituents, and the ring may be a carbocyclic or heterocyclic ring, aromatic ring, or non-aromatic ring; wherein the vicinal substituents comprise R.sup.3 and R.sup.7; a ring is formed between the geminal substituents from the same carbon, and the ring may be one or more of carbocyclic, heterocyclic ring, aromatic ring, or non-aromatic ring; wherein the geminal substituents from the same carbon comprise R.sup.9 and R.sup.10, R.sup.7 and R.sup.11; a bridged ring is formed between the non-geminal and non-vicinal substituents from different carbon atoms, or formed between the non-geminal and non-vicinal substituents from different nitrogen atoms, and the bridged ring may be carbocyclic or heterocyclic; isotopic substitutions of all elements are considered equivalent; the chiral center in the skeleton structure is either in the R configuration or the S configuration; and the chiral group on the substituent is either in the R configuration or the S configuration.

2. The compound according to claim 1, wherein the compound is represented by Formula (II): ##STR00166## wherein ring B is a fused ring formed by connecting any two adjacent positions of the ring A, which is any substituted or unsubstituted non-aromatic ring, non-aromatic heterocyclic ring, carboaromatic ring or aromatic heterocyclic ring.

3. The compound according to claim 1, wherein the compound is represented by Formula (III)-1 or Formula (III)-2: ##STR00167## wherein ring C is a five-membered ring structure, which is a five-membered carbocyclic ring or a five-membered heterocyclic ring; Y.sup.3 is N or CR.sup.4 or CR.sup.5; when one of X.sup.1 and X.sup.2 is absent and Y.sup.1 and Y.sup.2, or Y.sup.1 and Y.sup.3 are N, the ring A is neither a pyrrole ring nor 4-substituted pyrrole ring; two bonds of C—R.sup.12 and C—R.sup.13 from the same carbon do not form carbonyl or thiocarbonyl: R.sup.12 and R.sup.13 are H, CN, CF.sub.3, nitro, halogen, randomly substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclic group, optionally substituted alkoxy, optionally substituted alkylthio, optionally substituted alkylthio monoxide (sulfoxide), optionally substituted alkylthio dioxide (sulfone), optionally substituted sulfonyl, carboxylic acid, carboxylate, optionally substituted ester group, amide, optionally substituted amidoamino group, optionally substituted alkene group, optionally substituted cycloalkene group, optionally substituted arylalkyl group, optionally substituted heterocyclic arylalkyl group, optionally substituted aromatic hydrocarbon group, optionally substituted heterocyclic aromatic hydrocarbon group, optionally substituted aromatic olefin group, optionally substituted heterocyclic aromatic alkene group, wherein the substituent is selected from halogen, cyano, nitro, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio or C.sub.2-6 alkenyl, carboxyl, carboxylate, sulfonate.

4. The compound according to claim 1, wherein the compound is represented by Formula (IV)-1 or Formula (IV)-2: ##STR00168## wherein ring A and ring B are optionally substituted or unsubstituted non-aromatic ring, non-aromatic heterocyclic ring, carboaromatic ring or aromatic heterocyclic ring; ring C is a five-membered ring structure, which is a five-membered carbocyclic ring or a five-membered heterocyclic ring; Y.sup.3 is N, or CR.sup.4, or CR.sup.5; two bonds of C—R.sup.12 and C—R.sup.13 from the same carbon do not form carbonyl or thiocarbonyl; and R.sup.12 and R.sup.13 are H, CN, CF.sub.3, nitro, halogen, randomly substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclic group, optionally substituted alkoxy, optionally substituted alkylthio, optionally substituted alkylthio monoxide (sulfoxide), optionally substituted alkylthio dioxide (sulfone), optionally substituted sulfonyl, carboxylic acid, carboxylate, optionally substituted ester group, amide, optionally substituted amidoamino group, optionally substituted alkene group, optionally substituted cycloalkene group, optionally substituted arylalkyl group, optionally substituted heterocyclic arylalkyl group, optionally substituted aromatic hydrocarbon group, optionally substituted heterocyclic aromatic hydrocarbon group, optionally substituted aromatic olefin group, optionally substituted heterocyclic aromatic alkene group, wherein the substituent is selected from halogen, cyano, nitro, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio or C.sub.2-6 alkenyl, carboxyl, carboxylate, sulfonate.

5. The compound according to claim 1, wherein the compound is represented by Formula (V): ##STR00169## two bonds of C—R.sup.12 and C—R.sup.13 from the same carbon do not form carbonyl or thiocarbonyl; and; R.sup.12 and R.sup.13 are H, CN, CF.sub.3, nitro, halogen, randomly substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclic group, optionally substituted alkoxy, optionally substituted alkylthio, optionally substituted alkylthio monoxide (sulfoxide), optionally substituted alkylthio dioxide (sulfone), optionally substituted sulfonyl, carboxylic acid, carboxylate, optionally substituted ester group, amide, optionally substituted amidoamino group, optionally substituted alkene group, optionally substituted cycloalkene group, optionally substituted arylalkyl group, optionally substituted heterocyclic arylalkyl group, optionally substituted aromatic hydrocarbon group, optionally substituted heterocyclic aromatic hydrocarbon group, optionally substituted aromatic olefin group, optionally substituted heterocyclic aromatic alkene group, wherein the substituent is selected from halogen, cyano, nitro, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio or C.sub.2-6 alkenyl, carboxyl, carboxylate, sulfonate.

6. The compound according to claim 1, wherein the compound is represented by Formula (VI): ##STR00170## wherein ring A and ring B are optionally substituted or unsubstituted non-aromatic ring, non-aromatic heterocyclic ring, carboaromatic ring or aromatic heterocyclic ring; ring C is a five-membered ring structure, which is a five-membered carbocyclic ring or a five-membered heterocyclic ring; two bonds of C—R.sup.12 and C—R.sup.13 from the same carbon do not form carbonyl or thiocarbonyl; and R.sup.12 and R.sup.13 are H, CN, CF.sub.3, nitro, halogen, randomly substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclic group, optionally substituted alkoxy, optionally substituted alkylthio, optionally substituted alkylthio monoxide (sulfoxide), optionally substituted alkylthio dioxide (sulfone), optionally substituted sulfonyl, carboxylic acid, carboxylate, optionally substituted ester group, amide, optionally substituted amidoamino group, optionally substituted alkene group, optionally substituted cycloalkene group, optionally substituted arylalkyl group, optionally substituted heterocyclic arylalkyl group, optionally substituted aromatic hydrocarbon group, optionally substituted heterocyclic aromatic hydrocarbon group, optionally substituted aromatic olefin group, optionally substituted heterocyclic aromatic alkene group, wherein the substituent is selected from halogen, cyano, nitro, C.sub.1-6alkyl, C.sub.1-6haloalkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio or C.sub.2-6 alkenyl, carboxyl, carboxylate, sulfonate.

7. The compound according to claim 1, wherein the compound is represented by Formula (VII): ##STR00171## wherein ring A and ring B are optionally substituted or unsubstituted non-aromatic ring, non-aromatic heterocyclic ring, carboaromatic ring or aromatic heterocyclic ring: ring C is a five-membered ring structure, which is a five-membered carbocyclic ring or a five-membered heterocyclic ring; two bonds of C—R.sup.12 and C—R.sup.13 from the same carbon do not form carbonyl or thiocarbonyl; and R.sup.12 and R.sup.13 are H, CN, CF.sub.3, nitro, halogen, randomly substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclic group, optionally substituted alkoxy, optionally substituted alkylthio, optionally substituted alkylthio monoxide (sulfoxide), optionally substituted alkylthio dioxide (sulfone), optionally substituted sulfonyl, carboxylic acid, carboxylate, optionally substituted ester group, amide, optionally substituted amidoamino group, optionally substituted alkene group, optionally substituted cycloalkene group, optionally substituted arylalkyl group, optionally substituted heterocyclic arylalkyl group, optionally substituted aromatic hydrocarbon group, optionally substituted heterocyclic aromatic hydrocarbon group, optionally substituted aromatic olefin group, optionally substituted heterocyclic aromatic alkene group, wherein the substituent is selected from halogen, cyano, nitro, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio or C.sub.2-6 alkenyl, carboxyl, carboxylate, sulfonate.

8. The compound according to claim 1, wherein the compound is represented by one of the following formulae: ##STR00172## ##STR00173## ##STR00174## ##STR00175## ##STR00176## ##STR00177## ##STR00178## ##STR00179## ##STR00180## ##STR00181## ##STR00182## ##STR00183## ##STR00184## ##STR00185## ##STR00186## ##STR00187## ##STR00188## ##STR00189## ##STR00190## ##STR00191## ##STR00192##

9. A method for treating or preventing diseases comprising applying a compound of claim 1, wherein the diseases comprise one or more of the following: diseases related to the reproduction, replication or infection of one or more of Zika virus, dengue virus, flavivirus, West Nile virus and Chikungunya virus, hepatitis C, Japanese encephalitis, forest encephalitis, or AIDS caused by HIV.

10. A method for treating or preventing diseases caused by bacteria comprising applying the compound of claim 1.

11. The method of claim 10, wherein the diseases comprise diseases caused by Acinetobacter baumannii.

12. A pharmaceutical composition comprising the compounds, isomers or pharmaceutically acceptable salts of claim 1 as main active ingredients, supplemented by a pharmaceutically acceptable carrier.

Description

DETAILED DESCRIPTION

[0024] To make the above-mentioned objectives, features and advantages more easily be understood, the specific embodiments of the present invention will be described in detail below. Although the following descriptions illustrate in detail in order to facilitate understanding of the present invention, it should be understood by a skilled person in the art that the present invention can also be enabled by other ways not described herein. The skilled person in the art can also implement the present invention without departing from the spirit of the present invention such that the following descriptions concerning the examples will not limit the present invention. In addition, the expressions “an embodiment” or “an example” used herein refers to including specific features, structure and characteristics of at least one embodiment of the present invention. “According to an embodiment of the present invention” appears in the present disclosure does not necessarily mean that it refers to the same embodiment, or it does not necessarily mean that it independently or selectively contradicts with one another. It should be noted that the following embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be modified or equivalently replaced without departing from the spirit and scope of the technical solutions of the present invention, and all of them shall be covered by the scope of the claims of the present invention.

[0025] EXAMPLE 1: a method for preparing the compounds of the present invention, including:

##STR00028##

[0026] 2.74 ml of phenylhydrazine and 7.0 g of ZDL-5 were dissolved in 500 ml of DCM, and 5.3 ml of 2,6-lutidine was added, and finally 12.3 g of TBTU was added, and the mixture was stirred overnight at room temperature. The mixture was then purified to obtain about 7 g of ZDL-17.

##STR00029##

[0027] 600 mg of benzohydrazide and 1.39 g of ZDL-5 were dissolved in 100 ml of DCM, and 0.77 ml of 2,6-lutidine was added, and finally 2.12 g of TBTU was added, and the mixture was stirred overnight at room temperature. The mixture was then purified to obtain approximately 1.6 g of ZDL-27.

##STR00030##

[0028] ZDL-5 (500 mg) was dissolved in 50 ml DCM, and CDI (323 mg) was added under ice bath. The mixture was stirred for 20 minutes, and then hydrazine hydrate (0.55 ml) was added dropwise and stirred under ice bath for 2 hours.

##STR00031##

[0029] 850 mg of ZDL-26 was dissolved in 100 ml DCM, and 0.74 ml of pyridine was added under ice bath, and finally 815 mg of p-nitrobenzenesulfonyl chloride was added and the mixture was stirred at room temperature for 6 hours to obtain approximately 1.2 g of ZDL-29. After that, 250 mg of ZDL-29 was dissolved in 8 ml DCM, and 2 ml of TFA was added and the mixture was stirred at room temperature for 2 hours. After evaporating the reaction system by vacuum drying for 6 hours, 10 ml of toluene, 82 mg of p-nitrobenzaldehyde and 0.22 ml of triethylamine were added, and the mixture was reacted at 110° C. for 2 hours. The mixture then purified to obtain 90 mg of ZDL-38. After that, 150 mg of ZDL-29 was dissolved in 4 ml of DCM, and 1 ml of TFA was added and the mixture was stirred at room temperature for 2 hours. After evaporating the reaction system by vacuum drying for 6 hours, 10 ml of toluene, 95 mg of ZAL-2 and 0.16 ml of triethylamine were added, and the mixture was reacted at 110° C. for 2 hours. The mixture then purified to obtain 110 mg of ZDL-41.

##STR00032## ##STR00033##

[0030] 1.0 g of 1,2-cyclopentadicarboximide was dissolved in 50 ml of anhydrous THF under nitrogen protection, and 6.0 ml of phenylmagnesium bromide dropwise was then carefully added after fully cooling in an ice bath, and finally the mixture was stirred at room temperature for 3 hours. The mixture then purified to obtain 560 mg of crude ZDL-52. After that, 560 mg of ZDL-52 was dissolved in 40 ml of 1,2-dichloroethane, and 0.6 ml of TFA and 1.2 ml of triethylsilane were added and the mixture was reacted at 50° C. for 1 hour. The mixture then purified to obtain 400 mg of ZDL-53. After that, 100 mg of ZDL-53, 19 mg of copper(I) iodide and 323 mg of cesium carbonate into to a round-bottom flask. After being protected by N.sub.2, 20 ml of 1,4-dioxane, 80 μl of iodobenzene and 20 μl of N,N′-dimethylethylenediamine were added into the round-bottom flask in order. The mixture was reacted at 100° C. for 8 hours. The mixture then purified to obtain ZDL-60.

##STR00034##

[0031] 200 mg ZDL-53, 38 mg of copper(I) iodide and 647 mg of cesium carbonate into to a round-bottom flask. After being protected by N.sub.2, 20 ml of 1,4-dioxane, 371 mg of 4-nitroiodobenzene and 40 μl of N,N′-dimethylethylenediamine were added into the round-bottom flask in order. The mixture was reacted at 100° C. for 8 hours. The mixture then purified to obtain 120 mg of ZDL-61.

##STR00035##

[0032] 1.0 g of 1,2-cyclopentadicarboximide was dissolved in 50 ml of anhydrous THF under nitrogen protection, and 6.0 ml of 4-chlorophenylmagnesium bromide dropwise was then carefully added after fully cooling in an ice bath, and finally the mixture was stirred at room temperature for 3 hours. The mixture then purified to obtain 1 g of crude ZDL-58.

[0033] 1.0 g of ZDL-58 was dissolved in 40 ml of 1,2-dichloroethane, and 0.9 ml of TFA and 1.9 ml of triethylsilane were added and the mixture was reacted at 50° C. for 1 hour. The mixture then purified to obtain 500 mg of ZDL-59.

##STR00036##

[0034] 200 mg ZDL-59, 32 mg of copper(I) iodide and 552 mg of cesium carbonate into to a round-bottom flask. After being protected by N.sub.2, 20 ml of 1,4-dioxane, 140 l of iodobenzene and 40 μl of N,N′-dimethylethylenediamine were added into the round-bottom flask in order. The mixture was reacted at 100° C. for 8 hours. The mixture then purified to obtain 95 mg of ZDL-62.

[0035] 200 mg ZDL-59, 32 mg of copper(I) iodide and 552 mg of cesium carbonate into to a round-bottom flask. After being protected by N.sub.2, 20 ml of 1,4-dioxane, 316 mg of p-Nitroiodobenzene and 40 μl of N,N′-dimethylethylenediamine were added into the round-bottom flask in order. The mixture was reacted at 100° C. for 8 hours. The mixture then purified to obtain 70 mg of ZDL-63.

##STR00037##

[0036] 7.0 g of ZDL-5 was dissolved in 400 ml DCM, and 5.3 ml of N-methylimidazole was added under ice bath, and 2.06 ml of MsCl was added after stirring for 5 minutes, and then 3.66 g of p-nitrophenylhydrazine was added after stirring for another 30 minutes, and then the mixture was stirred overnight at room temperature. The mixture was then purified to obtain 6.5 g of ZDL-18.

##STR00038##

[0037] 300 mg of ZDL-18 was dissolved in 8 ml DCM, and 2 ml of TFA was added and the mixture was stirred at room temperature for 2 hours. After evaporating the reaction system by vacuum drying for 6 hours, 10 ml of toluene, 60 μl of 3,4-dimethoxybenzaldehyde and 0.32 ml of triethylamine were added, and the mixture was reacted at 110° C. for 2 hours. The mixture then purified to obtain 90 mg of ZDL-89.

##STR00039##

[0038] 200 mg of ZDL-28 was suspended in 10 ml of isopropanol, and then 123 mg of veratraldehyde and 2 drops of concentrated hydrochloric acid were added in order. The volatile components are removed after 8 hours of reaction at 85° C. The residue was chromatographed on a silica gel column with a DCM: EA system and passed through the column to obtain 150 mg of ZFD-33A.

##STR00040##

[0039] 12.5 g of ZXD-10 was dissolved in 100 mL of ethanol and stirred at 5° C., followed by adding 0.125 eq, 0.125 eq, 0.25 eq, 0.5 eq and 0.25 eq in five batches, totaling 1.25 eq of sodium borohydride. The reaction was stopped after a total of 6 hours. After that, 200 mL of water was added into the solution, and the pH was adjusted to weakly alkaline with solid carbonate. The solution was then extracted with DCM for several times, the organic phases were combined and dried over anhydrous sodium sulfate. 12.5 g of ZXD-15B product was obtained by column chromatography, which was a colorless liquid, and the yield was 48.0%. Finally, the unreacted ZXD-10 is recovered.

[0040] 16.2 g of ZXD-15B was dissolved in 250 mL of DCM, 21.4 g of solid sodium bicarbonate (3 equiv) was added, and 17.9 mL of Cbz-Cl (1.5 equiv) was added dropwise, after which the reaction was transferred to 30° C. for 9 hours and then stopped. After the solvent was evaporated, the crude product was diluted with ethyl acetate, then washed with NaHCO.sub.3 solution and dried. 25.6 g of ZXD-47 product was obtained by column chromatography, which was a colorless liquid, and the yield was 92.9%. 6 g of ZXD-47 was dissolved in a mixed solvent of methanol and water (36 mL: 24 mL), 960 mg (1.3 equiv) of solid sodium hydroxide was added, and the temperature was raised to 60° C. for reflux reaction. After 2 hours of reaction, it shows that the raw materials have reacted completely. Water was added into the solution after evaporating the methanol, and the pH of the system was adjusted to 1-2 with 1N HCl, and then concentrated to obtain 5.65 g of ZXD-60 foamed solid with a yield of 98.4%. ZXD-60 was dissolved in DCM and cooled at 0° C., and triethylamine (1.5 equiv) was added and stirred at the same temperature for 5 minutes. After that, isobutyl chloroformate (IBCF, 1.1 equiv) was added and stirred continuously at the same temperature for 1 hour. After the mixture is converted into active ester intermediates, phenylhydrazine (aniline or benzylamine) was added, and after stirring at 0° C. for 4 hours, it showed that all the intermediate conversion had stopped. The intermediates were diluted with DCM, and washed with saturated NaHCO.sub.3 solution and brine, and then dried over anhydrous sodium sulfate. After concentration, a mixed solvent of petroleum ether and ethyl acetate was used to stir and precipitate the product ZXD-51, which was a white solid with a yield of 93.9%.

[0041] ZXD-51 was dissolved in THF, and 10% palladium on carbon (0.05 equiv) was added. After vacuuming, a hydrogen balloon was inserted, and the reaction was carried out at 25° C. and stopped after 6 hours. After that, diatomaceous earth was used for suction filtration to remove palladium on carbon. After the mother liquor was evaporated, the product ZXD-44 was obtained by column chromatography, which was a white solid with a yield of 99.0%.

[0042] 250 mg of ZXD-44 and aldehyde (1.1 equiv) were dissolved in 10 mL of acetonitrile. TFA (1.0 equiv) was added under nitrogen protection, and the reaction was transferred to an oil bath preheated to 60° C. and refluxed. After 1.5 hours reaction, a product was formed on the spot plate, and the reaction of raw materials was basically completed and stopped. After the product was cooled to room temperature, saturated sodium bicarbonate solution was added to quench the reaction. The product was then diluted with ethyl acetate, then washed with NaHCO.sub.3 solution and brine and dried over anhydrous sodium sulfate. After concentration, ZXD-86B is separated by column chromatography, which was a white solid with a yield of 95.0%.

##STR00041##

[0043] 6 g of tetrahydroisoquinoline-3-carboxylic acid was dissolved in 50 ml of 1N NaOH, 50 ml of 1,4-dioxane was added, and 9 ml of (Boc).sub.2O was added dropwise under an ice bath, and reacted at room temperature for 4 hours. After the reaction is completed, dioxane is removed by distillation under reduced pressure, the system is adjusted to acidity with citric acid, and then extracted with EA, washed with saturated NaCl solution, and dried with anhydrous sodium sulfate. After the organic phase is evaporated to dryness, 7.8 g of transparent oily ZSD-2 can be obtained without purification.

[0044] 3.1 g of ZSD-2 was dissolved in 50 ml of DCM, and 1.4 g of p-nitroaniline and 124 mg of DMAP were added in an ice bath, then 2.1 g of DCC was added in batches and left at room temperature overnight. After the completion of the reaction, suction filtration was performed and the mother liquor was concentrated and then extracted with EA, washed with saturated NaCl solution, and dried with anhydrous sodium sulfate. Finally, recrystallization was performed to obtain 3.5 g of ZSD-4 product.

[0045] 250 mg of ZSD-4 was dissolved in 3 ml of DCM, 1 ml of trifluoroacetic acid was added and stirred at room temperature. The reaction was complete after stirring for 30 minutes. After that, the solvent was evaporated to dryness to obtain ZSD-5. ZSD-5 was dissolved in toluene, 0.3 ml of triethylamine and 113 mg of p-hydroxybenzaldehyde were added in order, and then refluxed at 110° C. for 1 hour. The mixture was extracted with EA, washed with saturated NaHCO.sub.3 and NaCl solutions, and dried with anhydrous sodium sulfate. After the completion of the drying, the solvent was concentrated and further separated and purified by column chromatography to obtain 150 mg of the target

##STR00042##

[0046] 5 g of ZSD-2 was dissolved in 50 ml of DCM, and 1.77 ml of phenylhydrazine and 220 mg of DMAP were added in an ice bath, then 3.72 g of DCC was added in batches and left at room temperature overnight. After the completion of the reaction, suction filtration was performed and the mother liquor was concentrated and then extracted with EA, washed with saturated NaCl solution, and dried with anhydrous sodium sulfate. Finally, recrystallization was performed to obtain 5.7 g of ZSD-14 product. 250 mg of ZSD-14 was dissolved in 3 ml of DCM, 1 ml of trifluoroacetic acid was added, and the reaction was complete after stirring at room temperature for 30 minutes. After the reaction, the solvent was evaporated to dryness to obtain ZSD-16 for later use. ZSD-16 was dissolved in toluene, 0.3 ml of triethylamine and 104 mg of p-hydroxybenzaldehyde were added in order, and then refluxed at 110° C. for 1 hour. The mixture was extracted with EA, washed with saturated NaHCO.sub.3 and NaCl solutions, and dried with anhydrous sodium sulfate. After the completion of the drying, the solvent was concentrated and further separated and purified by column chromatography to obtain 161 mg of the target product of ZSD-20.

[0047] The antibacterial ability of each specific compound (EC.sub.50 refers to the antiviral infection activity of the compound, among which Dengue virus: DENV; Zika virus: ZIKV; Usutu virus: USUV (usutu virus, which is a flavivirus that similar to Zika virus); AB: Acinetobacter baumannii) prepared by the above method is shown in the table below.

TABLE-US-00001 TABLE 1 anti-Zika virus and anti-Usutu virus activity (inhibition rate) Drug concentration (μM) Serial Compound Anti-USUV Anti-ZIKV number number 33 11 33 11 1 ZXP-10 + − 2 ZχP-12 + − 3 ZDL-11 + − − − 4 ZDL-19 +++ − + − 5 ZDL-21 − − + − 6 ZDL-38 + − − − 7 ZDL-39 − − + − 8 ZDL-41 / +++ / +++ 9 ZDL-42 / +++ / +++ 10 ZDL-43 +++ +++ +++ +++ 11 ZDL-60 + − + − 12 ZDL-61 +++ − + − 13 ZDL-62 +++ − + − 14 ZSD-7 +++ − +++ − 15 ZSD-8 − − +++ + 16 ZSD-9A + − +++ + 17 ZSD-11 + − +++ − 18 ZSD-12B + − − − 19 ZSD-18 + − + − 20 ZSD-20 + − +++ − 21 ZSD-27B + − − − 22 ZSD-30A +++ − − − 23 ZSD-32 + − − − 24 ZSD-36 + − − − 25 ZXD-51 − − + − 26 ZXD-53 − − + − 27 ZXD-62 + − +++ − 28 ZXD-72 − − + − 29 ZXD-86A − − +++ − 30 ZXD-86B +++ +++ +++ + 31 ZXD-95 + − / + 32 ZXD-102 − − / + 33 ZXD-107A − − / +++ 34 ZXD-121 − − / +++ 35 ZXD-126B +++ +++ / +++ 36 ZXD-131A / +++ / + 37 ZXD-131B / + − − 38 ZXD-140 +++ − / + 39 ZXD-147B / +++ / +++ 40 ZXD-156B / +++ / +++ 41 ZXD-157B / +++ 42 ZXD-176 +++ +++ / +++ 43 ZXD-178A / + / +++ 44 ZXD-178B / + / +++ 45 ZXD-181A + − +++ +++ 46 ZXD-241B +++ − +++ − +++: Complete suppression; +: Partial suppression; −: Inactive; /: Untested

TABLE-US-00002 TABLE 2 anti-Zika virus activity (EC.sub.50) Serial number Compound number EC.sub.50 (μM) 1 ZXD-142A 1.56 ± 0.21 2 ZXD-167 7.40 ± 0.37 3 ZXD-87A 3.40 ± 0.38 4 ZFD-33A + B 17.21

TABLE-US-00003 TABLE 3 anti- dengue virus activity (EC.sub.50, μM) Serial Compound number number EC.sub.50 1 ZBJ-12A 1.20 2 ZXD-44 1.50 3 ZXD-45 0.31 4 ZXD-52 0.059 5 ZXD-59 0.061 6 ZXD-70 0.18 7 ZXD-78A 0.17 8 ZXD-89A 0.74 9 ZXD-100A 2.00 10 ZXD-100B 0.85 11 ZXD-106 5.20 12 ZXD-107A 0.12 13 ZXD-116 2.30 14 ZXD-110 0.69 15 ZXD-112 0.48 16 ZXD-115 0.22 17 ZXD-116 2.30 18 ZXD-120A 6.60 19 ZXD-120B 6.5 20 ZXD-127B 5.20 21 ZXD-131A 3.60 22 ZXD-132A 0.64 23 ZXD-133A 19.50 24 ZXD-142A 1.60 25 ZDL-89 11.58 26 ZDL-93 24.84 27 ZDL-94 0.18

TABLE-US-00004 TABLE 4 anti-drug resistant strains of Acinetobacter baumannii (EC.sub.50, MIC (μg/mL)) Number of resistant strains of Serial Compound Acinetobacter baumannii number number no. 17 no. 18 no. 19 no. 20 1 ZXD-44 4 8 8 2 2 ZDL-101 4 4 4 2 3 ZFD-38 8 8 8 4 4 ZFD-42 4 4 4 1 5 ZXD-2-1 4 4 8 4 6 ZXD-7A 4 4 4 4 7 ZXD-7B 8 8 4 2 8 ZXD-8A 4 4 8 4 9 ZXD-8B 4 4 4 4 10 ZBM-5 2 2 1 2 11 ZBM-6 2 4 2 4 12 ZBM-8 2 4 2 4 13 ZBM-11 1 2 1 1 14 ZBM-15 1 2 1 2 15 ZBM-19 2 2 2 1 16 ZBM-20 0.5 1 0.5 0.5 17 ZBM-21 0.5 0.5 0.5 0.5 18 ZFD-44 0.5 1 1 1 19 ZSD-16 2 8 4 4 20 ZSD-28B >64 8 8 8 21 Positive drug 1 1 2 0.5 22

TABLE-US-00005 TABLE 5 anti-drug resistant strains of Acinetobacter baumannii (inhibition zone, diameter (mm)) Number of resistant strains of Serial Compound Acinetobacter baumannii number number no. 16 no. 17 no. 18 no. 19 no. 20 1 Blank 6 6 6 6 6 2 Positive control 6 6 6 6 6 3 ZBM-24 38 68 6 50 68 4 ZBM-28 51 68 64 64 68 5 ZBM-29 51 68 48 68 68 6 ZBM-30 45 68 45 68 68 7 ZBM-36 30 58 21 68 68 8 ZSD-54 50 58 47 68 68 9 ZXD-F 65 68 68 68 68 10 ZSD-15 44 40 68 68 40 11 ZKD-4A 58 40 66 68 62 12 ZKD-4B 68 68 68 68 68 13 ZKD-5A 68 68 68 68 68 14 ZKD-5B 68 48 48 55 68 15 ZKD-6A 45 43 20 25 64 16 ZKD-6B 16 17 16 20 40 17 ZKD-10A 56 53 55 48 68 18 ZKD-10B 39 48 45 46 54 19 ZKD-12A 65 68 68 58 68 20 ZKD-12B 68 68 55 60 68 21 ZKD-13A 68 68 68 64 68 22 ZKD-13B 68 68 36 64 68 23 ZKD-14A 68 68 45 64 68 24 ZKD-14B 54 53 34 68 68 25 ZKD-15A 46 50 40 68 68 26 ZKD-15B 67 68 40 68 68 27 ZKD-17 67 68 36 68 68 28 ZKD-18A 68 68 68 68 68 29 ZKD-18B 68 68 68 68 68 30 ZKD-19A 68 68 68 68 68 31 ZKD-19B 68 68 68 68 68 32 ZKD-21 60 48 53 64 68

TABLE-US-00006 TABLE 6 compound structures and their proton nuclear magnetic resonance spectrums (Z** represents the compound number) compound structures proton nuclear magnetic resonance spectrums [00043] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 9.99 (d, J = 3.9 Hz, 1H), 7.80 (d, J = 4.0 Hz, 1H), 7.13 (s, 1H), 7.03-6.85 (m, 2H, 6.74 (ddt, J = 5.1, 2.8 Hz, 2H). 6.61-6.41 (m, 2H), 5.56 (s, 1H), 4.12-3.97 (m, 1H), 3.72-3.51 (m, 2H). [00044] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 9.67 (d, J = 2.8 Hz, 1H), 7.69 (d, J = 2.7 Hz, 1H), 7.15-7.08 (m, 2H), 6.92-6.85 (m. 2H), 6.71- 6.66 (m, 3H), 6.60-6.55 (m, 1H), 6.81-6.42 (m, 1H), 3.92 (d, J = 3.1 Hz, 1H), 4.01-3.92 (m, 1H), 2.70-5.57 (m, 2H), 2.11-2.00 (m, 1H), 1.98-1.85 (m, 1H). [00045] DMSO-d.sub.6) δ 10.06 (s, 1H), 9.05 (s, 1H), 9.05 (s, 1H), 8.05 (d, J = 8.8 Hz, 2H), 6.94-6.86 (m, 2H), 6.75 (d, J = 9.0 Hz, 2H), 6.58 (d, J = 8.0 Hz, 1H), 6.51-6.46 (m, 1H), 6.01 (d, J = 2.9 Hz, 1H), 4.04-3.98 (m, 2H), 2.73-2.66 (m, 1H), 2.65-2.56 (m, 1H), 2.13- 2.61 (m, 1H), 1.97-1.89 (m, 1H). [00046] DMSO-d.sub.6) δ 9.91 (d, J = 2.5 Hz, 1H), 7.68 (d, J = 2.5 Hz, 2H), 7.45-7.34 (m, 5H), 7.35-7.33 (m, 1H), 7.21-7.13 (m, 1H), 7.15- 7.09 (m, 2H), 7.08-6.97 (m, 3H), 6.67-6.61 (m, 1H), 6.51 (d, J = 7.7 Hz, 2H), 5.28 (d, J = 12.7 Hz, 1H), 3.12 (d, J = 12.7 Hz, 1H), 4.96-4.87 (m, 1H), 2.70-2.64 (m, 1H), 2.63-2.57 (m, 1H), 2.40-2.29 (m, 1H), 1.85-1.75 (m, 1H). [00047] .sup.1H NMR (400 MHz, DMSO -D.sub.6) δ 10.77 (s, 1H), 8.22 (d, J = 9.2 Hz, 2H), 7.79 (d, J = 9.2 Hz, 2H), 7.77-7.61 (m, 1H), 7.30 (d, J = 7.7 Hz, 2H), 7.27-7.16 (m, 4H), 7.16-7.11 (m, 1H), 7.06- 6.97 (m, 1H), 5.23-5.09 (m, 2H), 4.89 (dd, J = 8.8, 7.1 Hz, 1H), 2.71-2.58 (m, 2H), 2.45-2.38 (m, 1H), 1.79-1.62 (m, 1H). [00048] (400 MHz, DMSO-d.sub.6) δ 8.28 (d, J = 8.7 Hz, 2H), 8.12 (s, 1H), 7.87 (d, J = 8.7 Hz, 2H), 7.11 (t, J = 7.4 Hz, 2H), 7.07 (d, J = 7.6 Hz, 1H), 6.91 (t, J = 7.5 Hz, 1H), 6.73 (t, J = 7.3 Hz, 1H), 6.66 (t, J = 7.3 Hz, 1H), 6.60 (d, J = 6.8 Hz, 2H), 6.13 (d, J = 8.1 Hz, 1H), 3.98 (d, J = 2.0 Hz, 1H), 4.59 (m, 1H), -2.89 (m, 2H), 2.34-2.31 (m, 1H), 1.68 (m, 1H). [00049] .sup.1H NMR (400 MHz, DMSO=d.sub.6 ) δ 10.28 (s, 1H), 9.06 (s, 1H), 7.91 (d, J = 8.7 Hz, 2H), 7.78-7.39 (m, 1H), 7.48-7.32 (m, 5H), 7.23-7.12 (m, 2H), 7.96-7.02 (m, 1H), 6.55 (d, J = 8.6 Hz, 2H), (d, J = 12.7 Hz, 1H), 5.17 (d, J = 12.7 Hz, 1H), 4.99-4.91 (m, 1H), 2.74-2.63 (m, 1H), 2.44-2.36 (m, 1H), 1.90-1.77 (m, 1H). [00050] (400 MHz, DMSO-d.sub.6) δ 9.55 (s, 1H), 7.84 (s, 1H), 7.20 (d, J = 8.3 Hz, 2H), 7.11 (t, J = 7.7 Hz, 2H), 6.97 (d, J = 7.3 Hz, 1H), 6.81-6.00 (m, 6H), 6.54 (m, 1H), 6.13 (d, J = 8.1 Hz, 1H), 5.95 (s, 1H), 4.17 (d, J = 11.4 Hz, 1H), 3.08-2.94 (m, 1H), 2.89 (dd, J = 17.0, 5.8 Hz, 1H), 2.39-2.31 (m, 1H), 2.00-1.85 (m, 1H). [00051] (400 MHz, DMSO-d.sub.6) δ 9.58 (s, 1H), 7.99 (s, 1H), 7.32 (d, J = 8.5 Hz, 2H), 7.19 (t, J = 7.7 Hz, 2H), 7.03 (d, J = 7.4 Hz, 1H), 6.93-6.87 (m, 1H), 6.78 (d, J = 8.5 Hz, 2H), 6.71 (t, J = 7.3 Hz, 1H), 6.63-6.57 (m, 3H), 6.23 (d, J = 8.1 Hz, 1H), 5.65 (d, J = 2.5 Hz, 1H), 4.48 (m, 1H), 2.98-2.82 (m, 1H), 2.32-2.28 (m, 1H), 1.62 (m, 1H). [00052] .sup.1H NMR (400 MHz, DMSO) δ 11.63 (s, 1H), 10.34 (d, J = 47.0 Hz, 1H), 7.91 (s, 1H), 7.64 (d, J = 8.0 Hz, 1H), 7.50 (dd, J = 34.5, 8.5 Hz, 1H), 7.27 (s, 1H), 7.21 (dd, J = 11.3, 4.0 Hz, 1H), 7.04 (dt, J = 17.7, 8.1 Hz, 3H), 6.83-6.73 (m, 2H). [00053] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 10.14 (s, 1H), 7.82-7.58 (m, 1H), 7.55 (d, J = 7.3 Hz, 2H), 7.34-7.16 (m, 8H), 7.14 (dd, J = 7.6, 1.6 Hz, 1H), 7.07-7.03 (m, 1H), 7.05-6.96 (m, 1H), 5.22-5.10 (m, 2H), 4.87 (dd, J = 8.8, 7.1 Hz, 1H), 2.73- 2.62 (m, 1H), 2.65-2.53 (m, 1H), 2.47-2.37 (m, 1H), 1.78- 1.66 (m, 1H). [00054] .sup.1H NMR (400 MHz, DMSO) δ 9.74 (d, J = 2.8 Hz, 1H), 7.74 (d, J = 2.7 Hz, 1H), 7.13 (t, J = 7.8 Hz, 2H), 7.04 (d, J = 7.2 Hz, 1H), 6.93 (t, J = 7.4 Hz, 1H), 6.70 (t, J = 8.9 Hz, 3H), 6.58 (t, J = 7.2 Hz, 2H), 6.00 (d, J = 3.0 Hz, 1H), 4.41-4.21 (m, 1H), 3.35-3.27 (m, 1H), 3.03 (dd, J = 16.0, 8.0 Hz, 1H). [00055] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 9.08 (s, 1H), 7.72 (s, 1), 7.08 (t, J = 7.7 Hz, 2H), 6.93 (s, 1H), 6.78 (d, J = 8.0 Hz, 1H), 6.74- 6.63 (m, 2H), 6.58 (d, J = 8.0 Hz, 2H), 4.84 (s, 1H), 3.73 (s, 3H), 2.95 (d, J = 9.9 Hz, 1H), 2.65 (d, J = 10.8 Hz, 1H), 2.26 (t, J = 10.5 Hz, 1H), 1.91 (dd, J = 34.6, 10.6 Hz, 2H), 1.60 (d, J = 11.6 Hz, 1H), 1.53-1.28 (m, 3H). [00056] (400 MHz, DMSO-d.sub.6) δ 8.05 (s, 1H), 7.36 (d, J = 8.3 Hz, 2H), 7.51 (D, J = 8.3 Hz, 2H), 7.11 (t, J = 7.4 Hz, 2H), 7.04 (d, J = 7.3 Hz, 1H), 6.90 (t, J = 7.7 Hz, 1H), 6.72 (t, J = 7.2 Hz, 1H), 6.62 (t, J = 7.4 Hz, 3H), 6.21 (d, J = 8.1 Hz, 1H), 5.79 (d, J = 2.1 Hz, 1H), 5.46 (s, 1H), 5.13 (s, 1H), 4.54 (d, J = 11.8 Hz, 1H), 2.99-2.84 (m, 2H), 2.35-2.30 (m, 1H), 2.11 (s, 3H), 1.65 (m, 1H). [00057] (400 MHz, DMSO-d.sub.6) δ 8.59 (s, 1H), 7.21-7.16 (m, 2H), 7.10- 7.01 (m, 3H), 6.98 (d, J = 7.2 Hz, 1H), 6.78 (t, J = 7.4 Hz, 1H), 6.74 (d, J = 8.4 Hz, 2H), 6.70 (d, J = 7.7 Hz, 2H), 6.67-6.58 (m, 2H), 5.31-5.26 (m, 1H), 3.15 (dd, J = 14.2, 3.3 Hz, 1H), 3.08 (dd, J = 14.1, 2.2 Hz, 1H), 2.86-2.78 (m, 1H), 2.74-2.65 (m. 1H), 2.61-2.52 (m, 1H), 2.62-1.94 *m, 1H), 1.40 (m, 1H), (s, 9H), 0.14 (s, 6H). [00058] .sup.1H NMR (400 MHz, Chloroform-d) δ 8.91-8.81 (s, 1H), 7.26- 7.19 (m, 5H), 7.16-7.10 (m, 1H), 6.95-6.88 (t, J = 7.4 Hz, 1H), 6.80-6.75 (d, J = 7.9 Hz, 2H), 6.18-3.97 (m, 1H), 4.11-4.05 (d, J = 4.9 Hz, 2H), 3.83-3.77 (dd, J = 9.7, 5.5 Hz, 1H), 3.31-3.19 (dd, J = 16.3,  Hz, 1H), 3.04-2.92 (dd, J = 16.3, 9.6 Hz, 1H). [00059] (400 MHz, DMSO-d.sub.6) δ 7.37 (d, J = 8.5 Hz, 2H), 7.33-7.19 (m, 3H), 7.12-7.07 (m, 2H), 6.99 (d, J = 7.3 Hz, 1H), 6.88 (d, J = 8.5 Hz, 2H), 6.86-6.81 (m, 1H), 6.57 ( , J = 7.4, 1.1 Hz, 1H), 6.18 (d, J = 7.9 Hz, 1H), 5.44 (d, J = 2.6 Hz, 1H), 4.75 (d, J = 15.5 Hz, 1H), 4.47 (m, 1H), 3.63 (d, J = 15.5 Hz, 1H), 2.95-2.77 (m, 2H), 2.37-2.26 (m, 1H), 1.50 (m, 1H), 0.94 (s, 9H), 0.19 (d, J = 1.0 Hz, 6H). [00060] .sup.1H NMR (400 MHz, DMSO) δ 9.69 (d, J = 3.3 Hz, 1H), 7.39 (dt, J = 15.6, 7.3 Hz, 6H), 7.31 (t, J = 7.0 Hz, 1H), 7.03 (d, J = 7.3 Hz, 1H), 6.94 (dd, J = 14.4, 6.7 Hz, 1H), 6.83 (d, J = 8.9 Hz, 2H), 6.68 (d, J = 8.9 Hz, 2H), 6.62-6.31 (m, 2H), 5.97 (d, J = 2.9 Hz, 1H), 4.99 (S, 2H), 4.38-4.22 (m, 1H), 3.31-3.20 (m, 1H), 3.01 (dd, J = 16.1, 7.9 Hz, 1H). [00061] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 9.76-9.69 (d, J = 3.1 Hz, 1H), 7.71-7.65 (d, J = Hz, 1H0, 7.02-6.94 (t, J = 8.9 Hz, 2H), 6.94- 6.83 (dd, J = 18.0, 7.7 Hz, 2H), 6.74-6.67 (m, 2H), 6.60-6.52 (m, 1H), 6.50-6.42 (m, 1H), 6.00 3.91 (d, J = 3.2 Hz, 1H), 4.00-3.90 (s, 1H0, 2.73-2.53 (m, 2H), 2.11-1.86 (m, 2H). [00062] .sup.1H NMR (400 MHz, Chloroform-d) δ 8.11-8.07 (d, J = 9.0 Hz, 2H), 7.25-7.15 (m, 3H), 6.64-6.58 (d, J = 9.0 Hz, 2H), 6.35-6.31 (s, 1H), 4.73-4.08 (d, J = 9.4 Hz, 2H), 3.92-3.85 (s, 1H), 3.28-3.18 (s, 1H), 3.10-3.00 (d, J = 7.8 Hz, 1H), 2.07-2.06 (s, 1H). [00063] .sup.1H NMR (400 MHz, DMSO-d.sub.6), δ 9.91 (d, J = 2.8 Hz, 1H), 8.90 (d, J = 2.2 Hz, 1H), 8.35-8.27 (m, 2H), 8.21 (d, J = 8.2 Hz, 1H), 7.72 (S, 2H), 6.97 (t, J = 8.7 Hz, 2H), 6.64 (dd, J = 9.0, 4.6 Hz, 2H), 5.05 (D, J = 3.6 Hz, 1H), 3.77 (d, J = 13.5 Hz, 1H), 3.53 (s, J = 12.8 Hz, 1H), 2.53 (s, 3H) 2.02 (d, J = 13.5 Hz, 1H), 1.50 (d, J = 12.7 Hz, 3H), 1.38-1.25 (m, 1H), 1.06 (s, 1H). [00064] .sup.1H NMR (400 MHz, Chloroform-d) δ 8.02-7.95 (d, J = 8.6 Hz, 2H), 7.49-7.43 (d, J = 8.9 Hz, 2H), 7.24-7.20 (m, 2H), 7.19-7.14 (S, 1H), 7.08-7.03 (d, J = 3.4 Hz, 1H), 6.99-6.92 (d, J = 10.2 Hz, 2H), 6.88-6.84 (d, J = 8.0 Hz, 1H), 5.92-3.61 (s, 1H), 4.19-4.10 (q, J = 7.2 Hz, 1H), 3.93-3.78 (m, 2H), 3.33-3.20 (d, J = 15.5 Hz, 1H), 3.16-3.02 (m, 1H). [00065] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 7.89 (s, 1H), 7.70-7.57 (m, 1H), 7.13-6.99 (m, 2H), 6.72-6.66 (m, 1H), 6.66-6.61 (m, 2H), 6.60 (dd, J = 3.2, 0.9 Hz, 1H), 6.43 (dd, J = 3.3, 1.8 Hz, 1H), 5.10 (s, 1H), 2.97 (d, J = 9.6 Hz, 1H), 2.73 (dd, J = 10.9, 3.7 Hz, 1H), 2.35 (t, J = 10.2 Hz, 1H), 1.88 (dd, J = 28.8, 10.2 Hz, 2H), 1.61 (d, J = 12.2 Hz, 1H), 1.39 (pd, J = 12.1, 6.1 Hz, 3H). [00066] .sup.1H NMR (400 MHz, Chloroform-d) δ 7.72-7.16 ( J = 13.2, 6.2 Hz, 6H), 7.06-7.01 (d, J = 7.1 Hz, 1H), 6.98-6.92 (z, J = 7.3 Hz, 1H), 6.82-6.77 (m, 3H), 6.73-6.68 (m, 1H), 3.94-5.74 (s, 1H), 4.02-3.91 (d, J = 14.1 Hz, 1H), 3.69-3.58 (d, J = 13.9 Hz, 1H), 3.37-3.27 (d, J = 10.5 Hz, 1H), 3.27-3.13 (m, 2H), 3.09-3.00 (d, J = 12.6 Hz, 1H), 2.95-2.84 (dd, J = 14.7, 6.1 Hz, 1H). indicates data missing or illegible when filed

TABLE-US-00007 TABLE 7 compound structures and their NMR mass spectra compound proton nuclear magnetic compound proton nuclear magnetic structures resonance spectrums structures resonance spectrums [00067] .sup.1H NMR (400 MHz, DMSO- d.sub.6) δ 7.75 (s, 1H), 7.08 (t, J = 7.7 Hz, 2H), 6.93 (d, J = 26.0 Hz, 3H), 6.67 (t, J = 7.3 Hz, 1H), 6.58 (d, J = 8.0 Hz, 2H), 4.90 (s, 1H), 3.73 (d, J = 5.2 Hz, 7H), 2.98 (s, 1H), 2.64 (d, J = 10.5 Hz, 1H), 2.28 (t, J = 10.5 Hz, 1H), 1.91 (dd, J = 36.4, 10.9 Hz, 2H), 1.59 (s,1H), 1.41 (d, J = 9.1 Hz, 2H). [00068] 1H NMR (400 MHz, DMSO) δ 10.34 (s, 1H), 8.19 (dd, J = 15.2, 8.8 Hz, 1H), 8.13-8.05 (m, 2H), 8.04- 7.97 (m, 1H), 7.76 (t, J = 8.3 Hz, 1H), 7.60 (qd, J = 7.0, 3.7 Hz, 3H), 7.22 (dd, J = 8.3, 7.5 Hz, 2H), 6.89 (d, J = 8.3 Hz, 2H). [00069] .sup.1H NMR (400 MHz, CDC1.sub.3) δ 7.48-7.41 (m, 1H), 7.38-7.31 (m, 2H), 7.20-7.11 (m, 2H), 6.66 6.59 (m, 4H), 4.98-4.96 (m, 1H), 3.68-3.63 (m, 1H), 3.49-3.46 (m, 1H), 2.06- 1.79 (m, 6H). [00070] .sup.1H NMR (400 MHz, DMSO-d) δ 8.07 (s, 2H), 7.82 (s, 1H), 7.77 (d, J = 7.6 Hz, 2H), 7.38 (d, J = 7.5 Hz, 2H), 7.06 (d, J = 8.3 Hz, 2H), 6.66 (1, J = 7.4 Hz, 1H), 6.57 (d, J = 8.0 Hz, 2H), 4.97 (s, 1H), 3.01 (s, 1H), 2.60 (d, J = 10.5 Hz, 1H), 2.33 (d, J = 9.7 Hz. 1H), 1.95 (d, J = 10.4 Hz, 1H), 1.86 (d, J = 9.5 Hz, 1H), 1.58 (s 1H), 1.42 (d, J = 18.9 Hz, 3H). [00071] .sup.1H NMR (400 MHz, Chloroform-d) δ 6.92 (dt, J = 11.0, 7.7 Hz, 4H), 6.78 (dd, J = 8.1, 1.9 Hz, 1H), 6.72 6.59 (m, 2H, 5.77 (s, 1H), 5.36 (d, J = 7.8 Hz, 2H), 3.90 (s, 3H), 3.66 (d, J = 11.5 Hz, 1H), 2.68 (dd, J = 63.4, 13.1 Hz, 2H), 2.11-1.87 (m, 2H), 1.46 (d, J = 12.8 Hz, 4H). [00072] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 8.04 (s, 1H), 7.69 (d, J = 7.6 Hz, 2H), 7.40 (d, J = 7.7 Hz, 2H), 7.13 (t, J = 7.7 Hz, 2H), 6.68 (dd, J = 33.2, 7.6 Hz, 3H), 5.50 (s, 1H), 2.65 (d, J = 13.8 Hz, 1H), 2.23 (t J = 12.3 Hz, 1H), 1.80 (t, J = 15.1 Hz, 3H), 1.60 (d, J = 10.5 Hz, 1H), 1.51 (d, J = 12.1 Hz, 1H), 1.39 (d, J = 13.3 Hz, 1H), 1.29 (s, 12H), 1.09-0.97 (m, 1H). [00073] .sup.1H NMR (400 MHz, DMSO) δ 10.03 (d, J = 3.2 Hz, 1H), 6.99 (t, J = 8.8 Hz, 2H), 6.74- 6.67 (m, 2H), 3.63-3.34 (m, 2H), 3.34-2.93 (m, 5H), 2.24 (m, 1H), 1.97 (m, 1H). [00074] .sup.1H NMR (400 MHz, DMSO) δ 11.85 (s, 1H), 8.42 (s, 1H), 8.20 (d, J = 8.5 Hz, 1H), 7.93- 7.79 (m, 4H), 7.6 8 (t, J = 7.7 Hz, 1H), 7.63-7.52 (m, 2H), 6.69 (s, 1H). [00075] Chloroform-d) δ 7.84 (d, J = 8.4 Hz, 2H), 7.26 (m, 3H), 7.16 (s, 1H), 7.12 (d, J = 7.3 Hz, 1H), 7.06 (t, J = 7.3 Hz, 1H), 6.72 (m, 1H), 5.37 5.18 (rn, 1H), 5.08 (s, 1H), 4.84 (d, J = 9.5 Hz, 1H), 4.07- 3.98 (m, 1H), 3.89 (d, J = 11.6 Hz, 1H), 3.43 (m, 1H), 3.13 (m, 2H), 2.82 (d, J = 16.3 Hz, 1H), 2.49 (d, J = 12.5 Hz, 1H), 2.18 (t, J = 12.1 Hz, 1H), 2.05 (d, J = 12.0 Hz, 1H), 1.87 (m, 1H), 1.76- [00076] (400 MHz, DMSO-d.sub.6) δ 8.49 (s, 1H), 7.19 (dd, J = 8.6, 7.3 Hz, 2H), 7.07 (td, J = 7.9, 1.6 Hz, 1H), 6.99 (d, J = 7.0 Hz, 1H), 6.83 (d, J = 8.2 Hz, 1H), 6.78 (t, J = 7.3 Hz, 1H), 6.75-6.69 (m, 4H), 6.65-6.60 (m, 2H), 5.29 (s, 1H), 3.71 (s, 3H), 3.56 (s, 3H), 3.18 (dd, J = 14.3, 3.5 Hz, 1H), 3.07 (dd, J = 14.2, 2.4 Hz, 1H), 2.99-2.93 (m, 1H), 2.72- 2.57 (m, 2H), 2.05- 1.66 (m, 2H), 1.63 1.53 2.01 (m, 1H), 1.41 (m, 1H). (m, 2H), 1.45 (t, J = 12.4 Hz, 1H), 1.32 (d, J = 20.1 Hz, 6H), 1.25 (s, 1H), 1.10 (s, 3H), 0.94 (s, 3H). [00077] .sup.1H NMR (400 MHz, DMSO- d.sub.6) δ 8.13 (s, 1H), 7.25 7.11 (m, 2H), 6.86-6.82 (m, 2H), 6.80-6.76 (m, 2H), 6.75-6.70 (m, 2H), 4.61(t, J = 4.9 Hz, 1H), 3.70 (d, J = 12.7 Hz, 6H), 2.90 (d = 5.0 Hz, 2H), 2.73 (d, J = 5.8 Hz, 2H), 1.66 (s, 1H), 1.33 (s, 3H), 1.38 (s, 2H), 1.24 (s, 1H). [00078] .sup.1H NMR (400 MHz, DMSO) δ 11.57 (s, 1H), 9.88 (d, J = 1.9 Hz, 1H), 7.82 (d, J = 2.0 Hz, 1H), 7.14 (t, J = 7.8 Hz, 2H), 6.93 (d, J = 11.3 Hz, 2H), 6.74 (d, J = 7.8 Hz, 2H), 6.70 (t, J = 7.3 Hz, 1H), 6.13 (d, J = 2.9 Hz, 1H). [00079] .sup.1H NMR (400 MHz, DMSO- d.sub.6) δ 7.81 (s, 1H), 7.67 (d, J = 7.7 Hz, 2H), 7.44 (d, J = 7.4 Hz, 2H), 7.07 (t, J = 7.6 Hz, 2H), 6.67 (t, J = 7.3 Hz, 1H), 6.57 (d, J = 8.0 Hz, 2H), 5.00 (s, 1H), 3.03 (s, 1H), 2.58 (d, J = 10.5 Hz, 1H), 2.33 (s, 1H), 1.96 (d, J = 10.3 Hz, 2H), 1.59 (d, J = 11.0 Hz, 1H), 1.42 (d, J = 18.8 Hz, 3H), 1.29 (s, 12H). [00080] .sup.1H NMR (400 MHz, DMSO) δ 9.78 (d, J = 3.0 Hz, 1H), 7.72 (d, J = 2.9 Hz, 1H), 7.05 6.91 (m, 4H), 6.75 6.67 (m, 2H), 6.63-6.46 (m, 2H), 6.00 (d, J = 3.0 Hz, 1H), 4.40- 4.24 (m, 1H), 3.31 (dd, J = 13.4, 7.7 Hz, 1H), 3.01 (dd, J = 15.9, 8.2 H7, 1H). [00081] .sup.1H NMR (400 MHz, DMSO) δ 12.20 (s, 1H), 9.43 (s, 1H), 8.09 (s, 2H), 7.54 (d, J = 8.3 Hz, 1H), 7.42-7.19 (m, 2H), 7.13- 7.04 (m, 1H), 6.90 (t, J = 12.3 Hz, 3H), 6.75 (s, 2H), 5.97 (s, 1H), 3.77-3.61 (m, 6H). [00082] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 11.56 (s, 1H), 9.91 (s, 1H), 7.80 (s, 1H), 7.23-6.87 (m, 4H), 6.74 (dd, J = 8.5, 4.6 Hz, 2H), 6.13 (s, 1H). [00083] .sup.1H NMR (400 MHz, Chloroform-d) δ 7.00-6.77 (m, 5H), 6.64-6.43 (m, 2H), 5.78 (s, 1H), 5.26 (s, 1H), 4.82 (d, J = 2.5 Hz, 1H), 4.14 (q, J = 7.1 Hz, 1H), 3.87 (s, 3H), 2.97 (dt, J = 11.2, 2.6 Hz, 1H), 2.81 (dd, J = 10.0, 3.6 Hz, 1H), 2.33-2.11 (m, 2H), 2.07 (s, 1H), 2.03- 1.94 (m, 1H), 1.69 (d, J = 3.6 Hz, 1H), 1.41 [00084] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 9.02 (s, 1H), 7.70 (s, 1H), 6.97-6.82 (m, 4H), 6.77 (d, J = 8.2 Hz, 1H), 6.57 (t, J = 6.6 Hz, 2H), 4.80(s, 1H). 3.74 (s, 3H), 2.95 (s, 1H), 2.62 (d, J = 10.6 Hz, 1H), 2.27 (d, = 11.2 Hz, 1H), 1.87 (s, 2H), 1.59 (s, 1H), 1.38 (t, J = 10.7 Hz, 3H). (dddd, J = 17.1, 12.9, 8.3, 4.1 Hz, 1H). [00085] .sup.1H NMR (400 MHz, DMSO) δ 8.43 (s, 1H), 8.33 (d, J 8.7 Hz, 2H), 7.92 (d, J = 8.7 Hz, 2H), 7.40 (d, J = 7.8 Hz, 1H), 7.29 (t, J = 8.6 Hz, 2H), 7.03 (d, J = 5.8 Hz, 1H), 6.96 (t, J = 7.8 Hz, 2H), 6.67 (t, J = 7.3 Hz, 1H), 6.26 (d, J = 7.81 Hz, 2H), 6.16 (s, 1H), 4.66 (dd, J = 8.8, 3.7 Hz, 1H), 3.32 (m, 2H). [00086] .sup.1H NMR (400 MHz, DMSO) δ 9.41 (s, 1H), 7.89 (d, J = 9.1 Hz, 2H), 7.30 (d, J = 7.2 Hz, 3H), 7.13 (d, J = 14.2 Hz, 2H), 7.03 (s, 2H), 6.36 (d, J = 8.2 Hz, 2H), 5.90 (s, 1H), 4.79 (s, 1H), 3.85-3.73 (m, 6H), 3.34-3.31 (m, 2H). [00087] .sup.1H NMR (400 MHz, DMSO) δ 9.42 (s, 1H), 7.86 (d, J = 8.9 Hz, 2H), 7.25 (t, J = 23.5 Hz, 4H), 7.04 (t, J = 8.2 HZ, 3H), 6.33 (d, J = 8.8 Hz, 2H), 5.87 (s, 1H), 4.72 (s, 1H), 3.78 (s, 3H), 3.33 (s, 2H), 0.94 (s, 9H), 0.22-0.04 (m, 6H). [00088] .sup.1H NMR (400 MHz, DMSO) δ 9.12 (s, 1H), 8.11 (d, J = 86.1 Hz, 1H), 7.27 (t, J = 6.3 Hz, 3H), 7.01-6.91 (m, 6H), 6.64 (t, J = 7.3 Hz, 1H), 6.25 (d, J = 7.8 Hz, 2H), 5.76 (s, 1H), 4.54 (dd, J = 8.3, 4.2 Hz, 1H), 3.80 (s, 3H), 3.31 (d, J = 8.7 Hz, 2H). [00089] (400 MHz, DMSO -d.sub.6) δ 8.68 (s, 1H), 7.96 (d, J = 8.7 Hz, 2H), 7.27-7.22 (m, 2H), 7.15 (t, J = 7.2 Hz, 1H), 7.04-6.99 (m, 3H), 6.94 (d, J = 7.9 Hz, 1H), 6.86- 6.82 (m, 3H), 6.75 (t, J = 7.3 Hz, 1H), 5.82-5.81 (m, 1H), 3.95 (dd, J = 11.8, 2.4 Hz, 1H), 3.60 (m., 1H), 3.19 (d, J = 15.8 Hz, 1H), 2.76 2.66 (m, 1H), 2.49-2.45 (m, 1H), 1.74-1.65 (m, 1H), −0.08 (m, 1H). [00090] (400 MHz, DMSO-d.sub.6) δ 8.66 (s, 1H), 8.14 (d, J = 8.6 Hz, 2H), 7.49 (d, J = 8.7 Hz, 2H), 7.19 (t, J = 7.9 Hz, 2H), 7.10 (t, J = 7.7 Hz, 1H), 7.01 (d, J = 7.0 Hz, 1H), 6.80 (t, J = 7.3 Hz, 1H), 6.75-6.65 (m, 4H), 5.43-5.41 (m, 1H), 3.44- 3.33 (m, 2H), 3.01 (d, J = 10.1 Hz, 1H), 2.72 2.60 (m., 2H), 2.04 1,99 (m, 1H), 1.38 (m, 1H). [00091] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.30 (d, J = 8.7 Hz, 2H), 7.58 (d, J = 8.8 Hz, 2H), 7.44- 7.16 (rn, 5H), 4.14 (q, J = 7.1 Hz, 1H), 3.83 3.68 (m, 2H), 3.29 (d, J = 17.9 Hz, 2H), 3.13 (s, 1H), 1.35 1.21 (m, 3H). [00092] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 0.09 (s, 1H), 8.08 (s, 1H), 7.18 7,12 (m, 2H), 6.92 (S, 1H), 6.65- 6.55 (m, 5H), 4.84 (s, 1H), 3.72 (s, 3H), 3.03 (d, J = 3.6 Hz 1H), 2.95 (d, J = 9.7 Hz, 1H), 2.72 (d, J = 5.4 Hz, 1H), 2.26 (t, J = 10.9 Hz, 1H), 1.95 (d, J = 10.7 Hz, 1H), 1.59 (t, J = 12.5 Hz, 3H), 1.32-1.21 (m, 3H). [00093] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 8.80 (s, 1H), 8.06 (s, 1H), 7.16 (t, J = 7.7 Hz, 2H), 6.75 (q, J = 7.8, 7.3 Hz, 2H), 6.69 (d, J = 7.9 Hz, 2H), 6.66-6.34 (m, 2H), 4.26 (s, 1H), 3.71 (s, 3H), 3.01 (d, J = 14.1 Hz, 1H), 2.78 (s, 2H), 2.62 (dd, J = 14.5, 6.3 Hz, 1H), 2.08 (s, 1H), 1.88-1.68 (m, 2H), 1.51 (t, J = 20.5 Hz, 2H), 1.26 (s, 2H). [00094] .sup.1NMR (400) MHz, DMSO-d.sub.6) δ 8.08 (s, 2H), 8.04 (s, 1H), 7.80 (d, J = 7.6 Hz, 2H), 7.34 (d, J = 7.6 Hz, 2H), 7.14 (t, J = 7.7 Hz, 2H), 6.72 (t, J = 7.5 Hz, 1H), 6.65 (d, J = 8.0 Hz, 2H), 5.48 (s, 1H), 2.68 (d, J = 11.8 Hz, 1H), 2.20 (t, J = 12.0 Hz, 1H), 1.79 (d, J = 12.8 Hz, 2H), 1.64-1.45 (m, 2H), 1.25 (d, J = 5.5 Hz, 3H). [00095] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 9.51 (s, 1H), 7.91 (s, 1H), 7.20 7.15 (m, 2H), 7.12 (t, J = 7.7 Hz, 2H), 6.75 (d, J = 8.4 Hz, 2H), 6.70 (t, J = 7.3 Hz, 1H), 6.63 (d, J = 8.0 Hz, 2H), 5.45- 5.18 (m, 1H), 2.65 (d, J = 14.0 Hz, 2H), 2.28 (t, J = 12.2 Hz, 1H), 1.80 (dd, J = 28.4, 12.2 Hz, 2H), 1.54 (dd, J = 32.0, 12.5 Hz, 2H), 1.36 (t, J = 14.7 Hz, 2H). [00096] .sup.1H NMR (400 MHz, DMSO) δ 9.16 (s, 1H), 8.23 (s, 1H), 7.28 (dd, J = 8.3, 5.5 Hz, 2H), 7.08 (d, J = 1.7 Hz, 1H), 6.96 (dd, J = 12.9, 5.4 Hz, 3H), 6.83 (d, J = 8.1 Hz, 1H), 6.71 (d, J = 8.7 Hz, 1H), 6.64 (t, J = 6.6 Hz, 1H), 6.58 (t, J = 7.2 Hz, 1H), 6.26 (d, J = 7.9 Hz, 2H), 5.79 (s, 1H), 4.63 (dd, J = 9.2, 3.0 Hz, 1H), 3.81 (s, 3H), 3.30 (d, J = 9.8 Hz, 2H). [00097] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 9.54 (s, 1H), 7.71 (s, 1H), 7.27 7.10 (m, 2H), 7.07 (t, J = 7.7 Hz, 2H), 6.79- 6.42 (m, 5H), 4.84 (s, 1H), 2.94 (d, J = 9.6 Hz, 1H), 2.62 (d, J = 10.4 Hz, 1H), 2.25 (t, J = 10.4 Hz, 1H), 1.94 (d, J = 10.1 Hz, 1H), 1.86 (d, J = 9.5 Hz, 1H), 1.60 (d, J = 11.6 Hz, 1H), 1.40 (d, J = 12.5 Hz, 3H). [00098] .sup.1H NMR (400 MHz, DMSO) δ 11.47 (s, 1H), 8.36 (d, J = 8.7 Hz, 2H), 8.09 (d, J = 8.8 Hz, 2H), 7.83 (d, J = 8.7 Hz, 2H), 7.57 (d, J = 8.0 Hz, 1H), 7.40 (t, J = 7.6 Hz, 1H), 7.32 (d, J = 8.8 Hz, 3H), 7.17 (t, J = 7.3 Hz, 1H), 6.36 (s, 1H), 4.38 (d, J = 9.1 Hz, 1H), 3.16 (dd, J = 16.2, 10.4 Hz, 1H), 2.91 (d, J = 15.9 Hz, 1H). [00099] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 10.39 (s, 1H), 9.47 (s, 1H), 7.00 (dd, J = 9.5, 7.7 Hz, 2H), 6.75 (ddd, J = 8.8, 4.6, 1.4 Hz, 2H), 3.22 (d, J = 12.8 Hz, 1H), 2.93 (d, J = 11.9 Hz, 1H), 2.21 (d, J = 12.7 Hz, 1H), 1.91 (s, 1H), 1.85 1.46 (m, 6H). [00100] .sup.1H NMR (400 MHz, DMSO) δ 11.25 (s, 1H), 9.68 (s. 1H), 8.07 (d, J = 8.8 Hz, 2H), 7.44 7.33 (m, 2H), 7.29 (dd, J = 8.6, 3.3 Hz, 5H), 7.12 (t, J = 7.0 Hz, 1H), 6.84 (d, J = 8.5 Hz, 2H), 6.07 (s, 1H), 4.33 (d, J = 9.4 Hz, 1H), 3.13 (dd, J = 16.2, 9.9 Hz, 1H), 2.87 (d, J = 16.3 Hz, 1H). [00101] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 7.92 (d, J = 7.8 Hz, 1H), 7.68 (d, J = 7.7 Hz, 2H), 7.49 (d, J = 7.6 Hz, 2H), 7.29 6.98 (m, 7H), 6.67 (dd, J = 22.1, 7.7 Hz, 3H), 5.26 (s, 1H), 3.83 (d, J = 14.3 Hz, 1H), 3.69 3.52 (m, 2H), 3.11 (dd, J = 15.8, 3.9 Hz, 1H), 3.05-2.86 (m, 1H), 1.28 (s, 13H). [00102] .sup.1H NMR (400 MHz, DMSO- d.sub.6) δ 9.07 (s, 1H), 7.94 (s, 1H), 7.14 (t, J = 7.7 Hz, 2H), 6.89 (s, 1H), 6.73 (d, J = 14.0 Hz, 3H), 6.65 (d, J = 7.9 Hz, 2H), 5.37 (s, 1H), 3.76 (s, 3H), 3.40 (d, J = 9.6 Hz, 1H), 2.69 (d, J = 11.7 Hz, 2H), 2.28 (t, J = 12.2 Hz, 1H), 1.80 (dd, J = 26.7, 12.8 Hz, 2H), 1.63-1.44 (m, 1H), 1.37 (t, J = 15.5 Hz, 2H). [00103] DMSO-d.sub.6) δ 11.23 (s, 1H), 8.39-8.25 (m, 4H), 7.98 (m, 4H), 7.34 7.15 (m, (3H, 7.00 (td, J = 7.1, 1.6 Hz, 1H), 6.14 (s, 1H), 4.85 (t, J = 6.7 Hz, 1H), 3.38 (d, J = 6.7 (Hz, 2H). [00104] .sup.1H NMR (400 MHz, DMSO) δ 9.81 (d, J = 2.8 Hz, 1H), 7.78- 7.64 (m, 3H), 6.97 (t, J = 8.9 Hz, 2H), 6.70 (dd, J = 8.9, 4.6 Hz, 2H), 3.70 (s, 3H) [00105] .sup.1H NMR (400 MHz, DMSO) δ 13.1 2 (s, 1H), 10.35 (s, 1H), 7.87 (s, 1H), 7.33 (s, 1H), 7.10 (s, 1H), 7.00 (dd, J = 16.8, 7.9 Hz, 2H), 6.73 (dd, J = 8.8, 4.6 Hz, 2H). [00106] .sup.1H NMR (400 MHz, DMSO) δ 10.18 (d, J = 2.5 Hz, 1H), 7.85 (d, J = 2.5 Hz, 1H), 7.77 (d, J = 34.4 Hz, 2H), 7.00 (t, J = 8.8 Hz, 2H), 6.82-6.71 (m, 2H), 3.79 (s, 3H). [00107] (400 MHz, DMSO-d.sub.6) δ 9.40 9.10 (m, 1H), 8.20- 7.70 (m, 2H), 7.70- 7.30 (m, 5H), 7.06 (d, J = 7.4 Hz, 1H), 6.90 (t, J = 7.7 Hz, 1H), 6.88 6.34 (m, 3H), 6.27 -6.07 (m, 1H), 5.95- 5.65 (m, 1H), 4.75- 4.55 (m, 1H), 3.01-2.86 (m, 2H), 2.34 2.26 (m, (1H, 1.90-1.50 (m, 1H). [00108] (400 MHz, DMSO-d.sub.6) δ 9.65 (s, 1H), 8.12 (d, J = 9.2 Hz, 2H), 7.32-7.24 (m, 3H), 7.22 7.20 (m, 2H), 7.08 (t, J = 7.6 Hz, 1H), 7.00 (d, J = 7.1 Hz, 1H), 6.86 (d, J = 9.2 Hz, 2H), 6.65 (t, J = 7.4 Hz, 2H), 5.42 (s, 1H), 3.27 (m, 1H), 3.11 (d, J = 14.1 Hz, 1H), 2.91 2.82 (m, 1H), 2.72 2.57 (m, 2H), 2.03-1.99 (m, 1H), 1.48 (m, 1H). [00109] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 9.55 (s, 1H), 7.83 (s, 1H), 7.29-7.23 (m, 3H), 7.21-7.11 (m, 3H), 7.11-7.05 (m, 3H), 6.77- 6.72 (m, 2H), 6.69 (t, J = 7.3 Hz, 1H), 6.64 (d, J = 7.9 Hz, 2H), 5.11 (s, 1H), 3.77 (d, J = 14.4 Hz, 1H), 3.66 (d, J = 14.4 Hz, 1H), 3.50 (d, J = 11.3 Hz, 1H), 3.10 (dd, J = 16.0, 3.8 Hz, 1H), 2.97 2.86 (m, 1H). [00110] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 8.23-8.14 (m, 2H), 7.87-7.81 (m, 2H), 7.27- 7.23 (m, 1H), 7.18 (dt, J = 11.7, 3.5 Hz, 3H), 7.04 (s, 1H), 6.95 (d, J = 1.2 Hz, 2H), 6.23 (d. J = = 1.2 Hz, 1H), 3.98 (dd, J = 9.2, 5.1 Hz, 1H), 3.91 (d, J = 14.7 Hz, 1H), 3.76 (s, 3H), 3.73 (s, 3H), 3.46 (d, J = 14.7 Hz, 1H), 3.12 (dd, 15.6, 5,2 Hz, 1H), 2.98 (dd, J = 15.5, 9.1 Hz, 1H). [00111] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 9.61 (s, 1H), 8.18 8.10 (m, 2H), 7.62 7.53 (m, 2H), 7.33 (d, J = 8.2 Hz, 2H), 7.27 (d, J = 7.2 Hz, 1H), 7.17 (dt, J = 15.9, 7.1 Hz, 2H), 7.09 (d, J = 7.2 Hz, 1H), 6.69 (d, J = 8.3 Hz, 2H), 5.67 (d, J = 2.1 Hz, 1H), 3.81 (d, J = 14.1 Hz, 2H), 3.08- 2.99 (m, 1H). [00112] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 8.12 (s, 1H), 7.73 (d J = 1.7 Hz, 1H), 7.15 (t, J = 7.7 Hz, 2H), 6.74 (t, J = 7.3 Hz, 1H), (6.66 (d, J = 7.9 Hz, 2H), 6.58 (d, J = 3.2 Hz, 1H), 6.47 (dd, J = 3.3, 1.8 Hz, 1H), 5.43 (s, 1H), 2.79 (dt, J =11.7, 3.5 Hz, 1H), 2.13 (td, J = 11.1, 3.8 Hz, 1H), 1.91-1.73 (m, 2H), 1.62 1.45 (m, 2H), 1.45 1.23 (m, 3H). [00113] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 9.00 (s, 1H), 7.71 (s, 1H), 7.08 (t, J = 7.6 Hz, 2H), 6.91 6.82 (m, 2H), 6.77 (d, J = 8.5 Hz, 1H), 6.67 (t, J = 7.3 Hz, 1H), 6.58 (d, J = 8.0 Hz, 2H), 4.82 (s, 1H), 3.75 (s, 3H), 2.96 (s, 1H), 2.63 (d, J = 10.7 Hz, 1H), 2.26 (t, J = 10.5 Hz, 1H), 1.98-1.79 (m, 2H), 1.61 (d, J = 11.5 Hz, 1H), 1.40 (q, J = 10.9, 9.0 Hz, 3H). [00114] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 9.01 (s, 1H), 7.92 (s, 1H), 7.13 (t, J = 7.7 Hz, 2H), 6.89 (d, J = 8.2 Hz, 1H), 6.82 (d, J = 21 Hz, 1H), 6.78- 6.67 (m, 2H), 6.65 (d, J = 7.78 Hz, 2H), 5.33 (d, J = 1.6 Hz, 1H), 3.76 (s, 3H), 3.39- 3.34 (m, 1H), 2.66 (d, J = 13.3 Hz, 1H), 2.27 (t, J = 12.2 Hz, 1H), 1.80 (dd, J = 26.2, 12.3 Hz, 2H), 1.62-1.52 (m, 1H), 1.49-1.26 (m, 3H). [00115] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 9.03 (s, 1H), 7.91 (s, 1H), 6.98 (t, J = 8.8 Hz, 2H), 6.89 (d, J = 8.2 Hz, 1H), 6.82 6.72 (m, 2H), 6.64 (dd, J = 8.9, 4.5 Hz, 2H), 5.32 (d, J = 1.6 Hz, 1H), 3.76 (s, 3H), 3.37 (s, 1H), 2.64 (d, J = 13.0 Hz, 1H), 2.27 (t, J = 12.3 Hz, 1H), 1.79 (dd, J = 27.6, 12.7 Hz, 2H), 1.61 1.50 (m, 1H), 1.47 (d, J = 12.3 Hz, 1H), 1.42 1.24 (m, 2H). [00116] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 7.97 (s, 1H), 7.14 (t, J = 7.6 Hz, 2H), 6.97- 6.83 (m, 3H), 6.72 (t, J = 7.4 Hz, 1H), 6.66 (d, J = 7.9 Hz, 2H), 5.42 (s, 1H), 3.75 (d, J = 2.2 Hz, 6H), 3.41 (d, J = 11.3 Hz, 1H), 2.69 (d, J = 12.4 Hz, 1H), 2.28 (t, J = 12.4 Hz, 1H), 1.81 (dd, J = 25.3, 12.6 Hz, 2H), 1.6 (d, J = 12.6 Hz, 1H), 1.51 (q, J = 11.0 Hz, 1H), 1.42 1.29 (m, 2H). [00117] .sup.1H NMR (400 MHz, DMSO) δ 11.91 (s. 1H), 10.49 (s, 1H), 8.01 (s, 1H), 7.74 (d, J = 1.6 (Hz, 1H), 7.45 (d, J = 8.7 Hz, 1H), 7.26 (d, J = 1.3 Hz, 1H), 7.21 (dd, J = 8.7, 2.0 Hz, 1H), 7.01 (t, J = 8.8 Hz. 2H), 6.86 6.72 (m, 2H). [00118] .sup.1H NMR (400 MHz, DMSO), δ 9.96 (s, 1H), 7.82 (s, 1H), 7.15 (d, J = 6.6 Hz, 3H), 6.97 (s, 1H), 6.83 6.66 (m, 3H), 6.60- 6.45 (m, 2H), 5.57 (s, 1H), 4.07 (d, J = 8.7 Hz, 1H), 3.61 (dd, J = 44.6, 35.2 Hz, 2H). [00119] .sup.1H NMR (400 MHz,) δ 8.07 (s, 1H), 7.15 (s, J = 7.7 Hz, (2H), 6.83-6.76 (m, 2H), 6.74 (td, J = 6.8, 6.3, 3.0 Hz, 2H), 6.70-6.65 (m, 2H), 4.32 (s, 1H), 3.70 (s, 3H), 3.61 (s, 3H), 3.05 (dd, J = 14.7, 3.6 (Hz, 1H), 2.91 (d, J = 10.2 Hz, 1H), 2.77 (dd, J = 14.7, 5.2 Hz, 2H), 2.35 ( 1H), 1.89- 1.75 (m, 2H), 1.59 (d, J = 13.0 Hz, 1H), 1.46 (d, J = 11.6 Hz, 1H), 1.33-1.21 (m, 2H). [00120] Chloroform-d), δ 7.80 (d, J = 8.7 Hz, 2H), 7.79-7.10 (m, 3H), 6.95 (m, 1H), 6.53 (d, J = 8.1 Hz, 1H), 6.23 (d, J = 8.7 Hz, 2H), 4.82 (d, J = 10.9 Hz, 2H), 4.37 (s, 1H), 4.31 (d, J = 10.7 Hz, 1H), 4.11 (d, J = 11.1 Hz, 1H), 3.42 (m, 2H), 3.35- 3.29(m, 1H), 3.25 (d, J = 11.4 Hz, 1H), 2.73 (s, 2H), 2.43 (d, J = 12.6 Hz, 1H), 1.98 (dd, J = 14.6, 8.7 Hz, 2H), 1.76 (s, 3H), 1.66 (t, J = 12.5 Hz, 2H), 1.38- 0.98 (m, 9H), 0.63 (s, 3H). [00121] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 9.04 (s, 1H), 8.21-8.09 (m, 2H), 7.65- 7.57 (m, 2H), 7.27 (d, J = 7.4 Hz, 1H), 7.23-7.07 (m, 3H), 7.01 (d, J = 8.5 Hz, 1H), 6.91-6.79 (m, 2H), 5.64 (d, J = 2.1 Hz, 1H), 3.81 (d, J = 14.3 Hz, 1H),  (s, 3H), 3.68 (S, 2H), 3.06-2.97 (m, 1H). [00122] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 8.33-8.21 (m, 2H), 7.93 (s, 1H), 7.6  (d, J = 8.7 Hz, 2H), 7.39 )dd, J = 8.4, 3.6 Hz. 3H), 7.31 (d, J = 7.0 Hz, 1H), 6.89 (t, J = 7.8 Hz, 2H), 6.63 (t, J = 7.3 Hz, 1H), 5.83 (d, J = 7.9 Hz, 2H), (d, J = 2.2 Hz, 1H), 4.26 (q, J = 3.5 Hz, 1H), 3.88 (s, 2H), 3.08 (d, J = 5.4 Hz, 2H). [00123] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 11.67 (s, 1H), 9.84 (s, 1H), 8.16 (d, J = 2.8 Hz, 1H), 8.10 (d, J = 7.9 Hz, 1H), 7.89-7.72 (m, 1H), 7.46 (d, J = 8.0 Hz, 1H), 7.14 (dt, J = 23.7, 7.3 Hz, 2H), 6.99 (t, J = 8.6 Hz, 2H), 6.81 (dd, J = 8.9, 4.7 Hz, 2H). [00124] .sup.1NMR (400 MHz, DMSO-d.sub.6) δ 10.46 (s, 1H), 8.23 (d, J = 9.3 Hz, 2H), 7.92 (d, J = 9.3 Hz, 2H), 6.94- 6.89 (m, 1H), 6.87 (d, J = 7.3 Hz, 1H), 6.63-6.36 (m, (1H, 6.53-6.44 (m, 1H), 6.03 (d, J = 2.4 Hz, 1H), 4.12- 4.03 (m, 1H), 2.77-2.65 (m, 1H), 2.65-2.56 (m, 1H), 2.12-1.97 (m, 2H). [00125] (400 MHz, DMSO-d.sub.6) δ 9.11 (s, 1H), 7.98 (s, 1H), 7.11 (t, J = 7.6 Hz, 2H), 7.03 (d, J = 7.5 Hz, 1H), 6.95- 6.87 (m, 4H), 6.72 (t, J = 7.4 Hz, 1H), 6.67-6.55 (m, 3H), 6.24 (d, J = 8.1 Hz, 1H), 5.62 (d, J = 2.6 Hz, 1H), 4.44 (d, J = 11.7 Hz, 1H), 3.77 (s, 3H), 3.85-2.90 (m, 1H), 2.90-2.80 (m, 1H), 2.35- 2.34 (m, 1H), 1.63 (m, 1H). [00126] (400 MHz, DMSO-d.sub.6) δ 8.13 (s, 1H), 8.08 (s, 1H), 8.06- 7.99 (m, 1H), 7.89-7.82 (m, 1H), 7.43-7.34 (m, 2H), 7.96 (d, J = 7.2 Hz, 3H), 6.92- 6.85 (m, 1H), 6.74-6.68 (m, 1H), 6.87-6.53 (m, (3H, 6.28 (d, J = 8.1 Hz, 1H), 6.25 (d, J = 2.6 Hz, 1H), 4.59 (d, J = 11.6 Hz, 1H), 3.04- 2.84 (m, 2H), 2.40-2.32 (m, 1H), 1.72 (m, 1H). [00127] Chloroform-d) δ 9.56 (s, 1H), 8.10 (d, J = 8.2 Hz, 2H), 7.84 (d, J = 8.4 Hz, 2H), 7.08 (d, J = 7.8 Hz, 2H), 6.87 (t, J = 7.5 Hz, 1H), 6.48 (d, J = 7.9 Hz, 1H), 4.99 (d, J = 10.7 Hz, 1H), 4.90 (s, 1H), 4.43 (s, 1H), 4.35 (s, 1H), 4.06 (d, J = 10.1 Hz, 1H), 3.38 (d, J = 16.5 Hz, 2H), 3.23 (d, J = 26.2 Hz, 3H), 3.70 (s, 2H), 2.44 (d, J = 12.7 Hz, 1H), 2.06-1.84 (m, 4H), 1.26-1.18 (m, 5H), 1.10 [00128] (400 MHz, DMSO-d.sub.6) δ 8.02 (s, 1H), 7.09- 7.03 (m, 4H), 6.99 (dd, J = 8.1, 2.1 Hz, 1H), 6.94- 6.89 (m, 1H), 6.82 (d, J = 8.0 Hz, 1H0, 6.70 (t, J = 7.3 Hz, 1H), 6.62 (m, 1H), 6.56 (d, J = 7.9 Hz, 2H), 6.26 (d, J = 8.0 Hz, 1H), 5.68 (d, J = 2.5 Hz, 1H), 4.54 (m, 1H), 3.72 (s, 3H), 3.90-2.83(m, 2H), 2.34-2.27 (m, (s, 3H), 0.81 (t, J = 6.5 1H), 1.62 (m, 1H), 8.94 Hz, 2H),  (s, 4H). (s, 9H), 8.10 (s, 6H). [00129] (400 MHz, DMSO-d.sub.6) δ 11.10 (s, 1H), 8.11 (s, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.28 (d, J = 1.8 Hz, 1H0, 7.19- 7.09 (m, 1H), 7.07 (d, J = 7.2 Hz, 1H), 6.94 (m, 1H), 6.74 (t, J = 7.3 Hz, 1H), 6.70- 6.57 (m, 3H), 6.18 (d, J = 8.1 Hz, 1H), 5.82 (d, J = 2.6 Hz, 1H), 4.49 (m, 1H), 3.01- 2.85 (m 2H), 2.35-2.28 (m, 1H), 1.66 (m, 1H). [00130] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 8.07 (s, 1H), 7.58 (d, J = 8.4 Hz, 2H), 7.48 (d, J = 8.4 Hz, 2H), 7.11 (t, J = 7.5 Hz, 2H), 7.05 (d, J = 7.3 Hz, 1H), 6.91 (t, J = 7.3 Hz, 1H), 6.72 (t, J = 7.3 Hz, 1H), 6.64 (d, J = 7.4 Hz, 1H), 6.59 (d, J = 7.0 Hz, 2H), 6.17 (d, J = 8.0 Hz, 1H), 5.81 (d, J = 1.9 Hz, 1H0, 4.54 (d, J = 11.9 Hz, (1H), 2.99-2.83 (m, 2H), 2.32-2.29 (m, 1H), 1.65 (m, 1H). [00131] (400 MHz, DMSO-d.sub.6δ 9.60 (s, 1H), 8.19 (d, J = 9.2 Hz), 2H), 7.92 (d, J = 9.2 Hz, 2H), 7.47 (d, J = 8.6 Hz, 2H), 7.03-6.95 (m, 2H), 6.71- 6.68 (m, 3H), 6.62 (td, J = 7.3, 1.7 Hz, 1H), - 6.57 (m, 1H), 4.71-4.87 (m, 1H), 2.95-2.78 (m, 2H), 2.33-2.38 (m, 1H), 1.66 (m, 1H). [00132] .sup.1H NMR (400 MHz, DMSO) δ 11.60 (d, J = 49.7 Hz, 1H), 9.81 (s, 1H), 8.15 (d, J = 13.8 Hz, 1H), 8.11 (d, J = 7.7 Hz, 1H), 7.79 (s, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.23-7.06 (m, (4H, 6.81 (d, J = 7.8 Hz, 2H), 6.70 (t, J = 7.3 Hz, 1H). [00133] (400 MHz, DMSO-d.sub.6) δ 9.73-9.68 (m, 1H), 8.15- 7.85 (m, 2H), 7.52- 7.36 (m, 2H), 7.05 (d, J = 7.2 Hz, 1H), 6.95-6.35 (m, 6H) 6.26-6.12 (m, 1H), 5.90-5.60 (m, 1H), 4.70- 4.50 (m, 1H), 3.01- 2.84 (m, 2H), 2.33-2.27 (m, 1H), 1.90-1.50 (m, 1H), 1.00-0.80 (m, 9H), 0.25-0.05 (m, 6H). [00134] (400 MHz, DMSO-d.sub.6) δ 9.75- 9.68 (m, 1H), 9.35-9.05 (m, 1H), 8.15-7.80 (m, 2H), 7.45-7.25 (m, 2H), 7.04 (d, J = 7.3 Hz, 1H), 6.90 (t, J = 7.6 Hz, 1H), 6.84- 6.37 (m, 5H), 6.30-6.10 (m, 1H), 5.85-3.55 (m, 1H), 4.70-4.45 (m, 1H), 3.00- 2.80 (m, 2H), 2.33-2.26 (m, 1H), 1.85-1.50 (m, 1H). [00135] (400 MHz, DMSO-d.sub.6) δ 8.05 (s, 1H), 7.52 (d, J = 7.8 Hz, 2H), 7.36 (d, J = 7.9 Hz, 2H), 7.10 (s, J = 7.4 Hz, 2H), 7.04 (d, J = 7.3 Hz, 1H), 6.92- 6.86 (m, 1H), 6.72 (t, J = 7.3 Hz, 1H), 6.67-6.47 (m, 3H), 6.21 (d, J = 8.1 Hz, 1H), 5.77 (d, J = 2.6 Hz, 1H), 4.73 (s, 2H), 4.54 (m, 1H), 3.04-2.81 (m, 2H), 2.36- 2.26 (m, 1H), 1.65 (m, [00136] (400 MHz, DMSO-d.sub.6) δ 8.05 (s, 1H), 7.49 (d, J = 7.9 Hz, 2H), 7.36 (d, J = 7.9 Hz, 2H), 7.11 (t, J = 7.6 Hz, 2H), 7.04 (d, J = 7.3 Hz, 1H), 6.91- 6.86 (m, 1H), 6.72 (t, J = 7.3 Hz, 1H), 6.63-6.59 (m, 3H), 6.21 (d, J = 8.1 Hz, 1H), 5.76 (d, J = 2.5 Hz, 1H), 5.25 (t, J = 5.7 Hz, 1H), 4.56- 4.50 (m, 3H), 3.00-2.83 (m, 2H), 2.33-2.28 (m, 1H), 1H),  (s, 9H), 0.08 (d, J = 1.65 (m, 1H). 1.3 Hz, 6H). [00137] (400 MHz, DMSO-d.sub.6) δ 8.16 (d, J = 9.1 Hz, 1H), 7.98 (d, J = 6.0 Hz, 2H), 7.64 (dd, J = 9.1, 6.5 Hz, 1H), 7.11 (t, J = 7.7 Hz, 2H), 7.04 (d, J = 7.3 Hz, 1H), 6.96 (m, 1H), 6.73 (t, J = 7.3 Hz, 1H), 6.66- 6.62 (m, 1H), 6.60 (d, J = 8.0 Hz, 2H), 6.52 (d, J = 8.1 Hz, 1H), 6.24 (d, J = 2.4 Hz, 1H), 4.57 (m, 1H), 2.98- 2.82 (m, 2H), 2.42-2.35 (m, 1H), 1.73 (m, 1H). [00138] (400 MHz, DMSO-d.sub.6) δ 8.04 (d, J = 9.0 Hz, 1H), 8.01- 7.94 (m, 1H), 7.90 (s, 1H), 7.59 (dd, J = 9.1, 6.6 Hz, 1H), 7.12 (t, J = 7.7 Hz, 2H), 6.93 (d, J = 7.4 Hz, 1H), 6.77-6.71 (m, 2H), 6.67 (d, J = 8.0 Hz, 2H), 6.55 (s, 1H),  J = 7.2 Hz, 1H), 6.40 (s, 1H), 4.38 (d, J = 10.9 Hz, 1H), 3.03-2.93 (m, 1H), 2.85 (dd, J = 16.9, 3.2 Hz, 1H), 2.46-2.35 (m, 1H), 2.31-2.24 (m, 1H). [00139] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 10.31 (s, 1H), 9.25 (s, 1H), 7.16 (t, J = 7.7 Hz, 2H), 6.77-6.67 (m, 3H), 3.25 (d, J = 11.0 Hz, 1H), 2.95 (d, J = 11.7 Hz, 1H), 2.22 (d, J = 13.0 Hz, 1H), 1.83 (d, J = 12.5 Hz, [00140] .sup.1H NMR (400 MHz, DMSO), δ 9.45 (s, 1H), 7.93 (s, 2H), 7.22 (t, J = 7.9 Hz, 2H), 7.06- 6.92 (m, 2H),  (s, 2H), 4.87 (s, 1H), 4.56 (t, J = 4.9 Hz, (2H, 3.51 (dd, J = 15.0, 5.2 Hz, 2H). 1H), 1.75-1.45 (m, 6H). [00141] (400 MHz, DMSO-d.sub.6) δ 8.07 (s, 1H), 7.54 (d, J = 6.7 Hz, 3H), 7.45-7.38 (m, 3H) 7.10 (t, J = 7.3 Hz, 2H), 7.04 (d, J = 7.2 Hz, 1H), 6.89 (t, J = 7.3 Hz, 1H), 6.71 (t, J = 7.3 Hz, 1H), 6.67-6.34 (m, 3H), 6.20 (d, J = 8.1 Hz, 1H), 8.78 (d, J = 2.1 Hz, 1H), 4.55 (d, J = 11.7 Hz, 1H), 2.98-2.83 (m, 2H), 2.36 2.27 (m, 1H), 1.65 (m, 1H). [00142] (400 MHz, DMSOd.sub.6) δ 9.28 (s, 1H), 8.53 (s, 1H), 7.18 (t, J = 7.9 Hz, 2H), 7.07 (td, J = 7.8, 1.5 Hz, 1H), 6.98 (t, J = 7.6 Hz, 3H), 6.78 (t, J = 7.3 Hz, 1H), 6.73-6.68 (m, 2H), 6.68-6.60 (m, 4H), 6.32- 5.23 (m, 1H), 3.06 (qd, J = 14.4, 2.7 Hz, 2H), 2.87 (d, J = 10.9 Hz, 1H), 2.72-2.98 (m, 2H), 2.05-1.98 (m, 1H, 1.38 (m, 1H). [00143] (400 MHz, DMSO-d.sub.6) δ 8.11 (s, 1H), 7.90-7.85 (m, 1H), 7.83-7.78 (m, 1H), 7.74 (s, 1H), 7.36- 7.29 (m, 2H), 7.15 (t, J = 7.8 Hz, 2H), 7.01 (d, J = 7.3 Hz, 1H), 6.83-6.72 (m, 4H), 6.62-6.55 ), 2H), 6.53 (d, J = 8.1 Hz, 1H), 4.25 (d, J = 11.0 Hz, 1H), 3.01 (m, 1H), 2.92 (dd, J = 17.1, 5.6 Hz, 1H), 2.39-2.32 (m, 1H), 2.03-1.88 (m, 1H). [00144] (400 MHz, DMSO-d.sub.6) δ 8.26 (s, 1H), 8.02 (d, J = 8.1 Hz, 1H), 7.69 (s, 1H), 7.64 (s, J = 7.6 Hz, 1H), 7.32 (t, J = 7.9 Hz, 1H), 7.13 (t, J = 7.9 Hz, 2H), 7.08 (d, J = 7.4 Hz, 1H), 7.00-6.94 (m, 1H), 6.74 (t, J = 7.4 Hz, 1H), 6.74-6.64 (m, 3H), 6.51 (d, J = 8.1 Hz, 1H), 6.34 (d, J = 2.4 Hz, 1H), 4.40 (m, 1H), 3.03-2.92 (m, 1H), 2.93-2.82 (m, 1H), 2.35-2.30 (m, 1H), 1.69 (m, 1H). [00145] (400 MHz), DMSO) δ 8.15 (d, J = 9.2, 2H) 7.59 (s, 1H), 7.57 (s, 2H), 6.76 (d, J = 3.2 Hz, 1H), 6.40-6.39 (m, 1H), 5.71 (d, J = 2.0 Hz, 1H), 3.02 (d, J = 10.4 Hz, 1H), 2.75 (d, J = 10.0 Hz, 1H), 2.35 (z, J = 10.8 Hz,  Hz, 1H), 1.99 (d, J = 10.8 Hz, 1H), 1.85 (d, J = 7.6 Hz, 1H), 1.61 (d, J = 9.2 Hz, 1H), 1.45 (d, J = 11.6 Hz, 1H), 1.38- 1.30 (m, 2H). [00146] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 10.36-10.25 (d, J = 3.1 Hz, 2H), 8.90-8.83 (s, 1H), 8.24-8.19 (d, J = 2.2 Hz, 1H), 8.10-8.07 (s, 1H), 8.04-8.01 (s, 1H), 7.79- 7.76 (d, J = 1.2 Hz, 1H), 7.62- 7.60 (d, J = 3.7 Hz, 2H), 7.60-7.57 (m, 3H), 6.97- 6.96 (s, 1H), 6.84-6.82 (s, 2H), 6.59-6.55 (d, J = 2.1 Hz, 1H), 6.51-6.46 (m, 1H), 5.29-5.21 (s, 1H), 3.75- 3.69 (s, 3H). [00147] .sup.1H NMR (400 MHz, DMSO) 8 & 14 (d, J = 9.2 Hz, 2H), 7.64 (d, J = 9.2 Hz, 2H), 7.82- 7.22 (m, 2H), 7.19 (t, J = 7.3 Hz, 1H), 7.11 (d, J = 7.3 Hz, 2H), 5.82 (t, J = 16.3 Hz, 1H), 3.27 (td, J = 9.2, 3.6 Hz, 1H), 3.14-3.1 (m, 1H), 2.09-1.80 (m, 2H0, 1.32- 1.37 (m, 2H), 1.21-0.93 (m, 2H). [00148] DMSO-d.sub.6) δ 7.39- 7.31 (m, 2H), 7.24 (t, J = 7.7 Hz, 4H), 7.18-7.13 (m, 1H), 7.13-7.08 (m, 2H), 7.04 (t, J = 7.3 Hz, 1H), 5.76 (d, J = 8.0 Hz, 1H), 3.18 (m, J = 9.2, 3.4 Hz, 1H), 3.05 (p, J = 8.3 Hz, 1H), 1.99 (m, J = 13.1, 6.7, 3.4 Hz, 1H), 1.89 (m, 1H), 1.43 (m, 2H), 1.08 (m, 2H). [00149] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 8.73 (s, 1H), 7.94 (s, 1H), 7.13 (t, J = 7.7 Hz, 2H), 6.81 (s, 1H), 6.74 (t, J = 9.5 Hz, 5H), 4.58 (s, 1H), 3.69 (s, 3H), 2.72 (s, 2H), 2.00 (s, 1H), 1.77 (d, J = 12.3 Hz, 1H), 1.33 (s, ), 1.18 (t, J = 7.1 Hz, 2H). [00150] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 8.80 (s, 1H), 8.19 (s, 1H), 7.20 (dd, J = 8.5, 7.2 Hz, 2H), 6.82- 6.53 (m, 7H), 4.52 (s, 1H), 3.73 (s, 4H), 2.82 (d, J = 5.1 Hz, 2H), 1.67 (s, 1H), 1.54 d), J = 10.6 Hz, 2H), 1.36 d), J = 15.2 Hz, 2H0, 1.27- 1.23 (m, 2H). [00151] (400 MHz, DMSO-d.sub.6δ 8.10 (s, 1H), 7.30 (s, J = 7.8 Hz, 1H), 7.15 (d, J = 7.6 Hz, 1H), 7.11-7.02 (m, 3H), 6.98 (z, J = 2.1 Hz, 1H), 6.91- 6.83 (m, 2H), 6.70 (s, J = 7.4 Hz, 1H), 6.62 (m, 1H), 6.55 (d, J = 6.8 Hz, 2H), 6.20 (d, J = 8.1 Hz, 1H), 5.72 (d, J = 2.6 Hz, 1H), 4.51 (m, 1H), 3.00-2.83 (m, 2H), 2.34- 2.25 (m, 1H), 1.63 (m, 1H), 0.92 (s, 9H), 0.13 (s, [00152] .sup.1H NMR (400 MHz, DMSO-d.sub.6(δ 8.02 (s, 1H), 7.72 (dd, J = 1.8, 0.8 Hz, 1H), 7.33- 7.22 (m, 5H), 6.97 (dd, J = 8.4, 7.2 Hz, 2H0, 6.69-6.62 (m, 1H), 6.57 (dd, J = 3.3, 0.9 Hz, 1H), 6.47 (dd, J = 3.3, 1.8 Hz, 1H0, 6.09 (d, J = 8.0 Hz, 2H), 5.57 (d, J = 8.1 Hz, 1H), 5.27 (d, J = 1.8 Hz, 1H), 4.03- 3.96 (m, 1H), 3.86 (d, J = 14.8 Hz, 1H), 3.70 (d, J = 14.8 Hz, 1H), 3.02 (qd, J = 15.2, 6.0 6H). Hz, 2H. [00153] (400 MHz, DMSO-d.sub.6) δ 8.05 (S, 1H), 7.42 (d, J = 8.5 Hz, 2H), 7.12-6.99 (m, 3H), 6.92-6.85 (m, 3H), 6.70 (t, J = 7.4 Hz, 1H), 6.61 (  J = 7.4, 1.1 Hz, 1H), 6.55 (d, J = 7.8 Hz, 2H), 6.20 (d, J = 8.2 Hz, 1H), 5.71 (d, J = 2.5 Hz, 1H), 4.55-4.46 (m, 1H), 2.99-2.83 (m, 2H), 2.33-2.27 (m, 1H), 1.62 (m, 1H), 0.94 (s, 9H), 0.18 (s, 6H). [00154] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 9.15 (s, 1H), 8.20-8.10 (m, 2H), 7.65-7.57 (m, 2H), 7.27 (d, J = 7.3 Hz, 1H), 7.23-7.06 (m, 3H), 7.03 (s, 1H), 6.97 (d, J = 8.1 Hz, 1H), 6.71 (dd, J = 8.1, 2.0 Hz, 1H), 5.63 (d, J = 2.1 Hz, 1H), 3.82 (d, J = 14.3 Hz, 1H), 3.72 (s, 1H), 3.69 (s, 3H), 3.61- 3.53 (m, 1H), 3.19 (dd, J = 13.8, 4.1 Hz, 1H), 3.13-3.01 (m, 1H). [00155] DMSO-d.sub.6) δ 7.38-7.32 (m, 2H), 7.32-7.28 (m, 2H), 7.28-7.22 (m, 2H), 7.18-7.10 (m, 2H), 7.65 (m, 1H), 5.77 (d, J = 8.0 Hz, 1H), 3.18 (m, 1H), 3.11- 2.98 (m, 1H), 2.04-1.84 (m, 2H), 1.43 (m, 2H), 1.20- 1.09 (m, 1H), 1.03 (m, 1H). [00156] DMSO-d.sub.6) δ 8.25-8.06 (m, 2H), 7.69-7.56 (m, 2H), 7.43-7.24 (m, 2H), 7.15 (d, J = 8.1 Hz, 2H), 5.85 (d, J = 8.0 Hz, 1H), 3.27- 3.23 (m, 1H), 3.10 (s, 1H), 1.95 (m, 2H), 1.44 (m, J = 7.1, 4.1 Hz, 2H), 1.15 (m, 1H), 1.04 (m, 1H). [00157] (400 MHz, DMSO-d.sub.6) δ 9.89 (s, 1H), 7.93 (s, 1H), 7.41 (dd, J = 7.8, 1.7 Hz, 1H), 7.18  J = 7.9, 1.7 Hz, 1H), 7.10 (s, J = 7.8 Hz, 2H), 7.01 (d, J = 7.4 Hz, 1H), 6.96-6.90 (m, 1H), 6.86-6.82 (m, 2H), 6.79 (t, J = 7.3 Hz, 1H), 6.64 (d, J= 7.8 Hz, 2H), 6.59 (m, 1H), 6.39 (d, J = 8.1 Hz, 1H), 6.05 (s, 1H), 4.41 (d, J = 9.5 Hz, 1H), 2.94-2.79 (m, 2H), 2.33-2.27 (m, 1H), 1.61 (m, 1H). [00158] (400 MHz, DMSO-d.sub.6) δ 7.89 (s, 1H), 7.30 (d, J = 8.5 Hz, 2H), 7.08 (t, J = 7.6 Hz, 2H), 6.98 (d, J = 7.3 Hz, 1H), 6.78 (d, J = 8.5 Hz, 2H), 6.75- 6.68(m, 2H), 6.62 (d, J = 7.9 Hz, 2H), 6.54 (m, 1H), 6.08 (d, J = 8.0 Hz, 1H) 5.99 (s, 1H), 4.18 (d, J = 11.5 Hz, 1H), 3.07- 2.95 (m, 1H), 2.90 (dd, J = 16.8, 5.8 Hz, 1H), 2.39- 2.33 (m, 1H), 1.95 (m, 1H), 0.90 (s, 9H), .013 (d, J = 1.4 Hz, 6H). [00159] (400 MHz, DMSO-d.sub.6) δ 9.50-9.10 (m, 1H), 8.40- 8.20 (m, 2H), 8.15-7.95 (m, 2H), 7.93-7.80 (m, 2H), 7.08 (d, J = 7.5 Hz, 1H 6.88-6.42 (m, 3H), 6.20- 5.90 (m, 2H), 4.80-4.55 (m, 1H), 3.01-2.87 (m, 2H), 2.35-2.29 (m, 1H), 1.90- 1.60 (m, 1H). [00160] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 9.92-9.68 (s, 1H), 7.74-7.70 (s, 1H), 7.16- 7.10 (d, J = 2.5 Hz, 3H), 7.08-7.02 (d, J = 3.8 Hz, 1H), 7.01-6.95 (t, J = 8.9 Hz, 2H), 6.74-6.68 (m, 2H), 4.02-3.86 (q, J = 16.5 Hz, 2H), 3.59-3.51 (dd, J = 9.8, 4.7 Hz, 1H), 2.96-2.76 (qd, J = 16.1, 7.2 Hz, 2H). [00161] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 9.20 (s, 1H), 7.88 (d, J = 8.9 Hz, 2H), 7.75 (s, 1H), 7.45-7.23 (m, 5H), 6.61 (d, J = 3.2 Hz, 1H), 6.48 (s, 1H), 6.10 (s, 1H), 5.33 (s, 1H), 4.08 (t, J = 5.6 Hz, 1H), 3.90 (d, J = 15.0 Hz, 1H), 3.74 (d, J = 14.9 Hz, 1H), 3.12-2.94 (m, 2H). [00162] .sup.1H NMR (400 MHz DMSO-d.sub.6) δ 8.99 (s, 1H), 7.80 (s, 1H), 7.25 (d, J = 7.4 Hz, 1H), 7.22-7.13 (m, 2H), 7.13- 7.06 (m, 3H), 6.89 (s, 1H), 6.74-6.60 (m, 5H), 5.03 (s, 1H), 3.72 (q, J = 14.4 Hz, 2H), 3.49 (d, J = 11.2 Hz, 1H), 3.10 (dd, J = 15.8, 3.9 Hz, 1H), 2.98- 2.84 (m, 1H). [00163] (400 MHz,DMSO-d.sub.6) δ 8.07 (S, 1H), 7.11-6.97 (m, 5H), 6.97-6.90 (m, 1H), 6.92-6.84 (m, 1H), 6.69 (t, J = 7.7 Hz, 1H), 6.61 (m, 1H), 6.58-6.47 (m, 2H), 6.20 (d, J = 8.1 Hz, 1H), 5.65 (s, 1H), 4.47 (m, 1H), 3.75 (s, 3H), 3.03-2.91 (m, 1H), 2.89-2.80 (m, 1H), 2.35-2.24 (m, 1H), 1.71-1.54 (m, 1H), 0.91 (s, 9H), 0.07 (s, 3H), 0.05 (s, 3H). [00164] (400 MHz, DMSO-d.sub.6) δ 8.24 (s, 1H), 8.01-7.93 (m, 1H), 7.88-7.82 (m, 1H), 7.68 (s, 1H), 7.42-7.35 (m, 2H), 7.12 (t, J = 7.6 Hz, 2H), 7.07 (d, J = 7.4 Hz, 1H), 6.95 (m, 1H), 6.73 (t, J = 7.3 Hz, 1H), 6.70-6.62 (m, 3H), 6.50 (d, J = 8.1 Hz, 1H), 6.28-6.17 (m, 1H), 4.39 (m, 1H), 3.01- 2.84 (m, 2H), 2.36-2.29 (m, 1H), 1.69 (m, 1H). indicates data missing or illegible when filed